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1
Sapak, Z., A. N. Mohd Faisol Mahadeven, Nurul Farhana M.H., Norsahira S., and Mohd Zafri A.W. "A review of common diseases of pineapple: the causal pathogens, disease symptoms, and available control measures." Food Research 5, S4 (November 26, 2021): 1–14. http://dx.doi.org/10.26656/fr.2017.5(s4).004.
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Pineapple is a perennial fruit-bearing tropical plant that belongs to the Bromeliaceae family, which has more than 2500 species. Pineapple is known excellent source of minerals and vitamins. It produces substantial calcium, potassium, glucose, the proteindigesting enzyme bromelain, fibre, vitamin A, B and C. In Malaysia, twelve registered varieties of pineapple have been introduced and commercially planted such as Moris (AC1), Sarawak (AC2), Gandul (AC3), Maspine (AC4), Josapine (AC5) Yankee (AC6) Moris Gajah (AC7), N36 (AC8), MD2 (AC9), View of Sunset (AC10), Madu Kaca (AC11), and Keningau Diamond (AC12). The disease is one of the important factors that can contribute to the huge losses of pineapple yield worldwide. This review paper aimed to discuss the main diseases of pineapple and their control management, particularly in Malaysia. The common diseases of pineapple that cause significant yield losses in the farms such as mealybug wilt-associated virus, bacterial heart rot, fruit collapse, butt rot, fruitlet core rot, black rot, yeasty and fusariosis are highlighted and discussed in detail on the causal pathogens, disease symptoms and signs, disease infection and development. The available control measures for managing pineapple diseases were also included in this paper.
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Alam, Md Amirul, Abdul Shukor Juraimi, M. Y. Rafii, Azizah Abdul Hamid, and Farzad Aslani. "Screening of Purslane (Portulaca oleraceaL.) Accessions for High Salt Tolerance." Scientific World Journal 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/627916.
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Purslane (Portulaca oleraceaL.) is an herbaceous leafy vegetable crop, comparatively more salt-tolerant than any other vegetables with high antioxidants, minerals, and vitamins. Salt-tolerant crop variety development is of importance due to inadequate cultivable land and escalating salinity together with population pressure. In this view a total of 25 purslane accessions were initially selected from 45 collected purslane accessions based on better growth performance and subjected to 5 different salinity levels, that is, 0.0, 10.0, 20.0, 30.0, and 40.0 dS m−1NaCl. Plant height, number of leaves, number of flowers, and dry matter contents in salt treated purslane accessions were significantly reduced (P≤0.05) and the enormity of reduction increased with increasing salinity stress. Based on dry matter yield reduction, among all 25 purslane accessions 2 accessions were graded as tolerant (Ac7 and Ac9), 6 accessions were moderately tolerant (Ac3, Ac5, Ac6, Ac10, Ac11, and Ac12), 5 accessions were moderately susceptible (Ac1, Ac2, Ac4, Ac8, and Ac13), and the remaining 12 accessions were susceptible to salinity stress and discarded from further study. The selected 13 purslane accessions could assist in the identification of superior genes for salt tolerance in purslane for improving its productivity and sustainable agricultural production.
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Jourdan, Karen B., Nicola A. Mason, Lu Long, Peter G. Philips, Martin R. Wilkins, and Nicholas W. Morrell. "Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries." American Journal of Physiology-Lung Cellular and Molecular Physiology 280, no. 6 (June 1, 2001): L1359—L1369. http://dx.doi.org/10.1152/ajplung.2001.280.6.l1359.
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Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca2+ and protein kinase C-activated but not Gi-inhibited pathways, supporting a role for AC2 and a Ca2+-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [3H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.
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Long, Qi, Ming-Hui Sun, Xiao-Xue Fan, Zong-Bing Cai, Kai-Yao Zhang, Si-Yi Wang, Jia-Xin Zhang, et al. "First Identification and Investigation of piRNAs in the Larval Gut of the Asian Honeybee, Apis cerana." Insects 14, no. 1 (December 23, 2022): 16. http://dx.doi.org/10.3390/insects14010016.
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Piwi-interacting RNAs (piRNAs), a class of small non-coding RNAs (ncRNAs), play pivotal roles in maintaining the genomic stability and modulating biological processes such as growth and development via the regulation of gene expression. However, the piRNAs in the Asian honeybee (Apis cerana) are still largely unknown at present. In this current work, on the basis of previously gained high-quality small RNA-seq datasets, piRNAs in the larval gut of Apis cerana cerana, the nominated species of A. cerana, were identified for the first time, followed by an in-depth investigation of the regulatory roles of differentially expressed piRNAs (DEpiRNAs) in the developmental process of the A. c. cerana. Here, a total of 621 piRNAs were identified in A. c. cerana larval guts, among which 499 piRNAs were shared by 4-(Ac4 group), 5-(Ac5 group), and 6-day-old (Ac6 group) larval guts, while the numbers of unique ones equaled 79, 37, and 11, respectively. The piRNAs in each group ranged from 24 nucleotides (nt) to 33 nt in length, and the first base of the piRNAs had a cytosine (C) bias. Additionally, five up-regulated and five down-regulated piRNAs were identified in the Ac4 vs. Ac5 comparison group, nine of which could target 9011 mRNAs; these targets were involved in 41 GO terms and 137 pathways. Comparatively, 22 up-regulated piRNAs were detected in the Ac5 vs. Ac6 comparison group, 21 of which could target 28,969 mRNAs; these targets were engaged in 46 functional terms and 164 pathways. The results suggested an overall alteration of the expression pattern of piRNAs during the developmental process of A. c. cerana larvae. The regulatory network analysis showed that piR-ace-748815 and piR-ace-512574 in the Ac4 vs. Ac5 comparison group as well as piR-ace-716466 and piR-ace-828146 in the Ac5 vs. Ac6 comparison group were linked to the highest number of targets. Further investigation indicated that targets of DEpiRNAs in the abovementioned two comparison groups could be annotated to several growth and development-associated pathways, such as the Jak/STAT, TGF-β, and Wnt signaling pathways, indicating the involvement of DEpiRNAs in modulating larval gut development via these crucial pathways. Moreover, the expression trends of six randomly selected DEpiRNAs were verified using a combination of stem-loop RT-PCR and RT-qPCR. These results not only provide a novel insight into the development of the A. c. cerana larval gut, but also lay a foundation for uncovering the epigenetic mechanism underlying larval gut development.
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Strait, Kevin A., Peter K. Stricklett, Mark Chapman, and Donald E. Kohan. "Characterization of vasopressin-responsive collecting duct adenylyl cyclases in the mouse." American Journal of Physiology-Renal Physiology 298, no. 4 (April 2010): F859—F867. http://dx.doi.org/10.1152/ajprenal.00109.2009.
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Little is known about collecting duct adenylyl cyclase (AC) isoforms or regulation in the mouse. We performed RT-PCR for AC isoforms 1–9 in microdissected cortical (CCD) and outer medullary (OMCD) and acutely isolated inner medullary (IMCD) collecting duct. All collecting duct regions contained AC3, AC4, and AC6 mRNA, while CCD and OMCD, but not IMCD, also contained AC5 mRNA. Acutely isolated IMCD expressed AC3, AC4, and AC6 proteins by Western blot analysis. The mIMCD3 cell line expressed AC2, AC3, AC4, AC5, and AC6 mRNA; M-1 CCD cells expressed AC2, 3, 4, and 6, while mpkCCD cell lines contained AC3, AC4, and AC6 mRNA. AVP stimulated cAMP accumulation in acutely isolated mouse IMCD; this was reduced by chelation of extracellular calcium (EGTA) and almost completely abolished by blockade of calmodulin (W-7). Blockade of calmodulin kinase with KN-93 or endoplasmic reticulum calcium ATPase (thapsigargin) also reduced the AVP response. A similar inhibitory effect of W-7, KN-93, and thapsigargin was seen on forskolin-stimulated cAMP content in acutely isolated mouse IMCD. These three agents had the same pattern of blockade of AVP- or forskolin-stimulated AC activity in acutely isolated rat IMCD. AVP responsiveness in primary cultures of mouse IMCD was also reduced by W-7, KN-93, and thapsigargin. Small interfering RNA (siRNA) designed to knock down AC3 or AC6 in primary cultured mouse IMCD significantly reduced AVP-stimulated cAMP accumulation. Together, these data are consistent with a role of AC3 and AC6 in the activation of mouse collecting duct by AVP.
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Yang, Jin, Xuhui Feng, Qiong Zhou, Wei Cheng, Ching Shang, Pei Han, Chiou-Hong Lin, Huei-Sheng Vincent Chen, Thomas Quertermous, and Ching-Pin Chang. "Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex." Proceedings of the National Academy of Sciences 113, no. 38 (September 6, 2016): E5628—E5635. http://dx.doi.org/10.1073/pnas.1525078113.
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Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.
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Lv, Yunyun, Yanping Li, Yunhai Yi, Lijun Zhang, Qiong Shi, and Jian Yang. "A Genomic Survey of Angiotensin-Converting Enzymes Provides Novel Insights into Their Molecular Evolution in Vertebrates." Molecules 23, no. 11 (November 9, 2018): 2923. http://dx.doi.org/10.3390/molecules23112923.
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Angiotensin-converting enzymes, ACE and ACE2, are two main elements in the renin–angiotensin system, with a crucial role in the regulation of blood pressure in vertebrates. Previous studies paid much attention to their physiological functions in model organisms, whereas the studies on other animals and related evolution have been sparse. Our present study performed a comprehensive genomic investigation on ace and ace2 genes in vertebrates. We successfully extracted the nucleotide sequences of ace and ace2 genes from high-quality genome assemblies of 36 representative vertebrates. After construction of their evolutionary tree, we observed that most of the phylogenetic positions are consistent with the species tree; however, certain differences appear in coelacanths and frogs, which may suggest a very slow evolutionary rate in the initial evolution of ace and ace2 in vertebrates. We further compared evolutionary rates within the entire sequences of ace and ace2, and determined that ace2 evolved slightly faster than ace. Meanwhile, we counted that the exon numbers of ace and ace2 in vertebrates are usually 25 and 18 respectively, while certain species may occur exon fusion or disruption to decrease or increase their exon numbers. Interestingly, we found three homologous regions between ace and ace2, suggesting existence of gene duplication during their evolutionary process. In summary, this report provides novel insights into vertebrate ace and ace2 genes through a series of genomic and molecular comparisons.
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Zhang, Ruifeng, Yingli Wu, Meng Zhao, Chuanxu Liu, Lin Zhou, Shaoming Shen, Shihua Liao, Kun Yang, Qingyun Li, and Huanying Wan. "Role of HIF-1α in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 297, no. 4 (October 2009): L631—L640. http://dx.doi.org/10.1152/ajplung.90415.2008.
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Angiotensin-converting enzyme (ACE) enhances the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which contribute to the pathogenesis of hypoxic pulmonary hypertension (HPH). Previous reports have demonstrated that hypoxia upregulates ACE expression, but the underlying mechanism is unknown. Here, we found that ACE is persistently upregulated in PASMCs on the transcriptional level during hypoxia. Hypoxia-inducible factor 1α (HIF-1α), a key transcription factor activated during hypoxia, was able to upregulate ACE protein expression under normoxia, whereas knockdown of HIF-1α expression in PASMCs inhibited hypoxia-induced ACE upregulation. Furthermore, HIF-1α can bind and transactivate the ACE promoter directly. Therefore, we report that ACE is a novel target of HIF-1α. Recently, a homolog of ACE, ACE2, was reported to counterbalance the function of ACE. In contrast to ACE, we found that ACE2 mRNA and protein levels increased during the early stages of hypoxia and decreased to near-baseline levels at the later stages after HIF-1α accumulation. Thus HIF-1α inhibited ACE2 expression, and the accumulated ANG II catalyzed by ACE is a key mediator in the downregulation of ACE2 by HIF-1α. Moreover, a reduction of ACE2 expression in PASMCs by RNA interference was accompanied by significantly enhanced proliferation and migration during hypoxia. We conclude that ACE is directly regulated by HIF-1α, whereas ACE2 is regulated in a bidirectional way during hypoxia and may play a protective role during the development of HPH. In sum, these findings contribute to the understanding of the pathogenesis of HPH.
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Afifah, Nisa Nur, Yani Mulyani, and Ari Yuniarto. "Review: Pengaruh Tanaman Obat Yang Beraktivitas Hipertensi Terhadap Ekspresi Gen Reseptor ACE-1 dan ACE 2." Jurnal Mandala Pharmacon Indonesia 7, no. 1 (June 30, 2021): 9–31. http://dx.doi.org/10.35311/jmpi.v7i1.64.
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Hipertensi adalah salah satu penyakit dengan angka kesakitan dan kematian yang terus meningkat, termasuk di Indonesia. Dalam mengatasi hipertensi obat-obatan seperti ACE inhibitor berperan dalam menurunkan tekanan darah diastol dan sistol, namun tanaman obat seperti ekstrak buah hawthorn, buah zaitun (Olea europaea L.), Hibiscus Sabdariffa, Allium Sativum dan Allium Cepa juga memiliki efek sebagai antihipertensi dengan harga yang relatif murah, mudah didapat, efek samping yang lebih rendah dibandingkan dengan obat sintesis atau kimia lainnya. Review jurnal ini ditujukan untuk mengetahui berbagai tanaman obat yang memiliki aktivitas hipertensi dan berpengaruh terhadap ekspresi gen reseptor hipertensi ACE1 dan ACE2. Penelusuran referensi dilakukan melalui database PubMed, Science Direct, dan Google Scholar, dengan kata kunci “Medicinal Plant”, “Gene expression”, “Angiotensin Converting Enzyme 1”, “Angiotensin Converting Enzyme 2”, dan“Antihypertension”. Tanaman obat digunakan sebagai terapi alternatif penurun tekanan darah tinggi dan merupakan salah satu cara pengobatan non farmakologis hipertensi. Hal ini menunjukkan bahwa tanaman obat memiliki pengaruh dalam menurunkan tekanan darah tinggi karena kandungan senyawa yang ada dalam masing-masing tanaman sehingga mampu menghambat reseptor hipertensi ACE1 dan ACE2 dengan berbagai metode ekspresi gen. Banyak tanaman obat yang telah diteliti memiliki aktivitas sebagai antihipertensi. Dari 14 tanaman obat dengan aktivitas sebagai anti hipertensi, sebanyak 90% tanaman berpengaruh terhadap ekspresi gen Angiotensin Converting Enzyme 1 (ACE 1), dan sebanyak 10% tanaman memiliki pengaruh terhadap Angiotensin Converting Enzyme 2 (ACE 2). Tanaman obat yang telah ditemukan dan memiliki aktivitas terhadap ekspresi gen Angiotensin Converting Enzyme 1 (ACE 1) paling banyak merupakan tanaman obat dengan family Poaceae, Oleaceae, dan Zingiberaceae.
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Alam, Md Amirul, Abdul Shukor Juraimi, M. Y. Rafii, and Azizah Abdul Hamid. "Effect of Salinity on Biomass Yield and Physiological and Stem-Root Anatomical Characteristics of Purslane (Portulaca oleraceaL.) Accessions." BioMed Research International 2015 (2015): 1–15. http://dx.doi.org/10.1155/2015/105695.
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13 selected purslane accessions were subjected to five salinity levels 0, 8, 16, 24, and 32 dS m−1. Salinity effect was evaluated on the basis of biomass yield reduction, physiological attributes, and stem-root anatomical changes. Aggravated salinity stress caused significant (P<0.05) reduction in all measured parameters and the highest salinity showed more detrimental effect compared to control as well as lower salinity levels. The fresh and dry matter production was found to increase in Ac1, Ac9, and Ac13 from lower to higher salinity levels but others were badly affected. Considering salinity effect on purslane physiology, increase in chlorophyll content was seen in Ac2, Ac4, Ac6, and Ac8 at 16 dS m−1salinity, whereas Ac4, Ac9, and Ac12 showed increased photosynthesis at the same salinity levels compared to control. Anatomically, stem cortical tissues of Ac5, Ac9, and Ac12 were unaffected at control and 8 dS m−1salinity but root cortical tissues did not show any significant damage except a bit enlargement in Ac12 and Ac13. A dendrogram was constructed by UPGMA based on biomass yield and physiological traits where all 13 accessions were grouped into 5 clusters proving greater diversity among them. The 3-dimensional principal component analysis (PCA) has also confirmed the output of grouping from cluster analysis. Overall, salinity stressed among all 13 purslane accessions considering biomass production, physiological growth, and anatomical development Ac9 was the best salt-tolerant purslane accession and Ac13 was the most affected accession.
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Soós, B., M. Fagyas, Á. Horváth, E. Végh, A. Pusztai, M. Czókolyová, A. Csongrádi, et al. "AB0062 ANGIOTENSIN CONVERTING ENZYME ACTIVITY IN ANTI-TNF-TREATED RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS PATIENTS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1164.1–1164. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1001.
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BackgroundAngiotensin-converting enzyme (ACE) and ACE2 have been implicated in the regulation of vascular physiology. Elevated synovial and decreased or normal ACE or ACE2 levels have been found in rheumatoid arthritis (RA). Very little is known about the effects of tumour necrosis factor α (TNF-α) inhibition on ACE or ACE2 homeostasis.ObjectivesIn this study, we assessed the effects of one-year anti-TNF therapy on ACE and ACE2 production in RA and ankylosing spondylitis (AS) in association with other biomarkers.MethodsForty patients including 24 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 16 AS patients treated with ETN were included in a 12-month follow-up study. Serum ACE levels were determined by commercial ELISA, while serum ACE2 activity was assessed using a specific quenched fluorescent substrate. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. In addition, CRP, rheumatoid factor (RF) and ACPA were also measured. All assessments were performed at baseline and 6 and 12 months after treatment initiation.ResultsAnti-TNF therapy increased ACE levels in the full cohort, as well as in the RA and AS subsets. ACE2 activity increased in the full cohort, while the ACE/ACE2 ratio increased in the full cohort and in the RA subset (p<0.05). Uni- and multivariable regression analyses determined associations between ACE or ACE/ACE2 ratios at different time points and disease duration, CRP, RF, FMD and IMT (p<0.05). ACE2 activity correlated with CRP. The changes of ACE or ACE2 over 12 months were determined by treatment together with either RF or FMD (p<0.05).ConclusionAnti-TNF treatment may increase ACE and ACE2 in the sera of RA and AS patients. ACE and ACE2 may be associated with disease duration, markers of inflammation and vascular pathophysiology. The effects of TNF inhibition on ACE and ACE2 may reflect, in part, the effects of these biologics on the cardiovascular system.Disclosure of InterestsBoglárka Soós: None declared, Miklós Fagyas: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Anita Pusztai: None declared, Monika Czókolyová: None declared, Alexandra Csongrádi: None declared, Attila Hamar: None declared, Zsófia Pethö: None declared, Nóra Bodnár: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Éva Szekanecz: None declared, Szilvia Szamosi Speakers bureau: Roche, Sager, Amgen, Sándor Szántó Speakers bureau: AbbVie, Novartis, Lilly, MSD, UCB, Consultant of: AbbVie, Novartis, UCB, Gabriella Szücs Speakers bureau: Roche, Lilly, Actelion, Zoltán Papp: None declared, Zoltán Szekanecz Speakers bureau: AbbVie, Pfizer, Roche, MSD, Novartis, Lilly, Richter, Consultant of: Pfizer, Novartis, Richter, Grant/research support from: Pfizer, UCB
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Herath, Chandana B., John S. Lubel, Zhiyuan Jia, Elena Velkoska, David Casley, Lindsay Brown, Chris Tikellis, Louise M. Burrell, and Peter W. Angus. "Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2." American Journal of Physiology-Gastrointestinal and Liver Physiology 297, no. 1 (July 2009): G98—G106. http://dx.doi.org/10.1152/ajpgi.00045.2009.
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Angiotensin converting enzyme (ACE) 2 activity and angiotensin-(1-7) [Ang-(1-7)] levels are increased in experimental cirrhosis; however, the pathways of hepatic Ang-(1-7) production have not been studied. This study investigated the role of ACE2, ACE, and neutral endopeptidase (NEP) in the hepatic formation of Ang-(1-7) from angiotensin I (Ang I) and Ang II and their effects on portal resistance. Ang I or Ang II were administered to rat bile duct ligated (BDL) and control livers alone and in combination with the ACE inhibitor lisinopril, the ACE and NEP inhibitor omapatrilat, or the ACE2 inhibitor MLN4760 ( n = 5 per group). BDL markedly upregulated ACE, ACE2, and NEP. Ang-(1-7) was produced from Ang II in healthy and in BDL livers and was increased following ACE inhibition and decreased by ACE2 inhibition. In contrast, Ang-(1-7) production from Ang I was minimal and not affected by ACE or NEP inhibition. Surprisingly, ACE2 inhibition in BDLs dramatically increased Ang-(1-7) production from Ang I, an effect abolished by ACE2/NEP inhibition. Ang II and Ang I induced greater portal pressure increases in BDL livers than controls. The effects of Ang I were closely correlated with Ang II production and were strongly attenuated by both ACE and ACE/NEP inhibition. These findings show that the major substrate for hepatic production of Ang-(1-7) is Ang II and this is catalyzed by ACE2. Ang I is largely converted to Ang II by ACE, and net conversion of Ang I to Ang-(1-7) is small. NEP has the ability to generate large amounts of Ang-(1-7) in the BDL liver from Ang I only when ACE2 activity is greatly decreased or inhibited.
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Soler, María José, Minghao Ye, Jan Wysocki, Josette William, Josep Lloveras, and Daniel Batlle. "Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan." American Journal of Physiology-Renal Physiology 296, no. 2 (February 2009): F398—F405. http://dx.doi.org/10.1152/ajprenal.90488.2008.
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Angiotensin-converting enzyme (ACE)2 is a carboxypeptidase that degrades angiotensin II and other peptides. In the kidney, ACE2 localization within the glomerulus and tubules is cell specific. This study was aimed to investigate the localization of ACE2 within the renal vasculature. We also studied the effect of the administration of a specific angiotensin II type 1 receptor blocker, telmisartan, on ACE2 expression in the renal vasculature. ACE2 and ACE were localized in renal arterioles using confocal microscopy and specific cell markers. Quantitative measurements of ACE2 and ACE mRNA were estimated in kidney arterioles isolated by laser capture microdissection using real-time PCR. In kidney arterioles, ACE was localized in the endothelial layer, whereas ACE2 was localized in the tunica media. In mice treated with telmisartan (2 mg·kg−1·day−1) for 2 wk, ACE2 expression was increased by immunostaining, whereas ACE expression was decreased. This was reflected in a decrease in the ACE/ACE2 ratio compared with vehicle-treated controls (0.53 ± 0.14 vs. 7.59 ± 2.72, P = 0.027, respectively). In kidney arterioles isolated by laser capture microdissection, the ACE/ACE2 mRNA ratio was also decreased compared with control mice (1.21 ± 0.31 vs. 4.63 ± 0.86, P = 0.044, respectively). In conclusion, in kidney arterioles ACE2 is preferentially localized in the tunica media, and its expression is increased after administration of the angiotensin II type 1 receptor blocker, telmisartan. Amplification of ACE2 in the renal vasculature may contribute to the therapeutic action of telmisartan by increasing angiotensin II degradation.
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Hariyanto, Timotius Ivan, Karunia Valeriani Japar, Vika Damay, Felix Kwenandar, Novia Lauren Sieto, and Andree Kurniawan. "The Use of ACE inhibitor/ARB in SARS-CoV-2 Patients: A Comprehensive Narrative Review." Asian Journal of Medical Sciences 11, no. 6 (November 1, 2020): 113–20. http://dx.doi.org/10.3126/ajms.v11i6.29911.
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The three most common comorbidities that are associated with increased mortality in COVID-19 patients are Hypertension, Diabetes, and Cardiovascular disease, Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARB) are the drugs most commonly prescribed for the management of these diseases. Recent experimental study in animals and humans have found that SARS-CoV-2 uses ACE2 as the receptors for entry. Moreover, in an animal study, the use of ACE inhibitor/ARB increases the level of ACE2 expression that can lead to increased SARS-CoV-2 infectivity. On the other side, some evidences suggest that the ACE2 receptor is not necessary for SARS-CoV-2 entry into the cell and suggested that there is a cofactor that play part. Experimental studies in humans also showed that there is no association between ACE inhibitor/ARB with SARS-CoV-2 infectivity and mortality. In conclusion, there is still insufficient data to stop the use of inhibitor/ARB in SARS-CoV-2 patients. Therefore, we suggested that in line with the recommendations from ESC and AHA/ACC, the use of these two drugs in SARS-CoV-2 patients with cardiovascular comorbidity should still be continued.
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Li, Bing, Yan Hong Wang, Ju Mei Wang, and Wei De Shen. "Cloning and Expression Analysis of Acetylcholinesterase Gene (Bm-ace1, Bm-ace2) from Domesticated Silkworm, Bombyx mori." Advanced Materials Research 175-176 (January 2011): 13–18. http://dx.doi.org/10.4028/www.scientific.net/amr.175-176.13.
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Acetylcholinesterase (AChE, 2 EC 3.1.1.7), encoded by the ace gene, catalyzes the hydrolysis of the neurotransmitter acetylcholine to terminate nerve impulses at the postsynaptic membrane. In this study, AChE genes (Bm-ace1, Bm-ace2) were cloned from domesticated silkworm Bombyx mori (Dazao strain) through RT-PCR. Sequence analysis showed that the ORF of Bm-ace1 gene contained 2 025 bp nucleotides, encoding 683 amino acid residues. The predicted protein has a molecular weight (MW) of 76.96 kD and an isoelectric point (pI) of 6.36; The ORF of Bm-ace2 gene contained 1 917 bp nucleotides, encoding 638 AA’s. The predicted protein has a MW of 71.68 kD and a pI of 5.49. These two acetylcholinesterase genes both contain conserved motifs including a catalytic triad, a choline-binding site and an acyl picket. A clustering analysis showed that Bm-ace1 (ABY50088)shared highest similarity with Bmm-ace1 (ABM66370) from Chinese wild silkworm (B. mandarina), Bm-ace2 (ABY50089) shared highest similarity with Bm-ace2 (NP_001037366) from B. mori. Using semi-quantitative RT-PCR, expression analyses in insect tissues and in development period demonstrated that Bm-ace1and Bm-ace2 were expressed highly in head and fat bodies; Bm-ace1 and Bm-ace2 were expressed firstly higher, then lower and higher again from 1st instar to 5th instar stages. Bm-ace1 was expressed higher than that of Bm-ace2 in all the stages. This result will help understanding of the resistance mechanism of B. mori to organophosphosphorous insecticides.
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RICE, Gillian I., Daniel A. THOMAS, Peter J. GRANT, Anthony J. TURNER, and Nigel M. HOOPER. "Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism." Biochemical Journal 383, no. 1 (September 24, 2004): 45–51. http://dx.doi.org/10.1042/bj20040634.
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In the RAS (renin–angiotensin system), Ang I (angiotensin I) is cleaved by ACE (angiotensin-converting enzyme) to form Ang II (angiotensin II), which has effects on blood pressure, fluid and electrolyte homoeostasis. We have examined the kinetics of angiotensin peptide cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin). The activity of the enzyme preparations was determined by active-site titrations using competitive tight-binding inhibitors and fluorogenic substrates. Ang I was effectively cleaved by NEP to Ang (1–7) (kcat/Km of 6.2×105 M−1·s−1), but was a poor substrate for ACE2 (kcat/Km of 3.3×104 M−1·s−1). Ang (1–9) was a better substrate for NEP than ACE (kcat/Km of 3.7×105 M−1·s−1 compared with kcat/Km of 6.8×104 M−1·s−1). Ang II was cleaved efficiently by ACE2 to Ang (1–7) (kcat/Km of 2.2×106 M−1·s−1) and was cleaved by NEP (kcat/Km of 2.2×105 M−1·s−1) to several degradation products. In contrast with a previous report, Ang (1–7), like Ang I and Ang (1–9), was cleaved with a similar efficiency by both the N- and C-domains of ACE (kcat/Km of 3.6×105 M−1·s−1 compared with kcat/Km of 3.3×105 M−1·s−1). The two active sites of ACE exhibited negative co-operativity when either Ang I or Ang (1–7) was the substrate. In addition, a range of ACE inhibitors failed to inhibit ACE2. These kinetic data highlight that the flux of peptides through the RAS is complex, with the levels of ACE, ACE2 and NEP dictating whether vasoconstriction or vasodilation will predominate.
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Kar, Sumit, Lie Gao, and Irving H. Zucker. "Exercise training normalizes ACE and ACE2 in the brain of rabbits with pacing-induced heart failure." Journal of Applied Physiology 108, no. 4 (April 2010): 923–32. http://dx.doi.org/10.1152/japplphysiol.00840.2009.
Full textAbstract:
Exercise training (EX) normalizes sympathetic outflow and plasma ANG II in chronic heart failure (CHF). The central mechanisms by which EX reduces this sympathoexcitatory state are unclear, but EX may alter components of the brain renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) may mediate an increase in sympathetic nerve activity (SNA). ACE2 metabolizes ANG II to ANG-(1–7), which may have antagonistic effects to ANG II. Little is known concerning the regulation of ACE and ACE2 in the brain and the effect of EX on these enzymes, especially in the CHF state. This study aimed to investigate the effects of EX on the regulation of ACE and ACE2 in the brain in an animal model of CHF. We hypothesized that the ratio of ACE to ACE2 would increase in CHF and would be reduced by EX. Experiments were performed on New Zealand White rabbits divided into the following groups: sham, sham + EX, CHF, and CHF + EX ( n = 5 rabbits/group). The cortex, cerebellum, medulla, hypothalamus, paraventricular nucleus (PVN), nucleus tractus solitarii (NTS), and rostral ventrolateral medulla (RVLM) were analyzed. ACE protein and mRNA expression in the cerebellum, medulla, hypothalamus, PVN, NTS, and RVLM were significantly upregulated in CHF rabbits (ratio of ACE to GAPDH: 0.3 ± 0.03 to 0.8 ± 0.10 in the RVLM, P < 0.05). EX normalized this upregulation compared with CHF (0.8 ± 0.1 to 0.4 ± 0.1 in the RVLM). ACE2 protein and mRNA expression decreased in CHF (ratio of ACE2 to GAPDH: 0.3 ± 0.02 to 0.1 ± 0.01 in the RVLM). EX increased ACE2 expression compared with CHF (0.1 ± 0.01 to 0.8 ± 0.1 in the RVLM). ACE2 was present in the cytoplasm of neurons and ACE in endothelial cells. These data suggest that the activation of the central RAS in animals with CHF involves an imbalance of ACE and ACE2 in regions of the brain that regulate autonomic function and that EX can reverse this imbalance.
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Badaras, Ignas, and Agnė Laučyė-Cibulskienė. "COVID-19 POVEIKIS ENDOTELIUI." Health Sciences 5, no. 32 (August 1, 2022): 113–15. http://dx.doi.org/10.35988/sm-hs.2022.204.
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Neseniai buvo iškelta idėja, kad COVID-19 gali būti laikoma endotelio liga. SARS-CoV- 2 patenka į ląsteles, naudodamas S baltymą, kuris atpažįsta angiotenziną konvertuojantį fermentą- 2 (angl. angiotensine-converting enzyme, ACE2). ACE2 randami epitelyje, plonosios žarnos enterocituose, arterijų miocituose ir kardiovaskulinės sistemos endotelyje. COVID-19 sukeltos endoteliopatijos lygis koreliuoja su ligos sunkumu. ACE ir ACE2 receptoriai veikia antagonistiškai. ACE2 skatina vazodilataciją, mažina uždegimą ir oksidacinį stresą. ACE veikia vazokonstriktiškai, skatina uždegimą ir oksidacinį stresą. COVID-19 metu mažėja ACE2 kiekis, sutrinka pusiausvyra tarp ACE ir ACE2 poveikio, labiau pasireiškia ACE efektai. COVID-19 metu endotelio pažaidą sukelia tiesioginiai ir netiesioginiai veiksniai. Tiesioginiai veiksniai – dėl viruso sumažėjęs ACE2 kiekis bei imuninių ląstelių poveikis infekuotoms endotelio ląstelėms. Netiesioginiai veiksniai žaloja endotelį dėl hiperaktyvaus uždegiminio atsako ir padidėjusios citokinų koncentracijos. Įrodymų dėl ilgalaikio COVID-19 poveikio kraujagyslėms nėra, bet aprašyti galimi pažaidos mechanizmai, skatinantys endotelio remodeliaciją ir fibrozę.
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Camargo Junior, Otacílio de, Luiz Roberto Felizzola, Antonio Cláudio Guedes Chrispim, Claudio Roberto Cabrini Simões, Márcia Fayad Marcondes, Marivan Pedra Araújo, Kelly Cristina Moraes, and Márcio Villar de Freitas. "Enxerto subclávio-carotídeo como método de tratamento na obstrução da artéria carótida comum." Jornal Vascular Brasileiro 9, no. 1 (2010): 78–81. http://dx.doi.org/10.1590/s1677-54492010000100014.
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A oclusão isolada da artéria carótida comum (ACC) é uma lesão relativamente incomum (0,5 a 5%). A maioria dos pacientes com obstrução da ACC tem lesão concomitante na artéria carótida interna (ACI) e na artéria carótida externa (ACE) ipsilaterais, sendo que, ocasionalmente, a circulação colateral da ACE pode preservar a perviedade da ACI via fluxo retrógrado. Relatamos o caso de um paciente sintomático com oclusão da ACC e perviedade das ACI e ACE tratado cirurgicamente com enxerto subclávio-carotídeo.
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Wysocki, Jan, Anne Goodling, Mar Burgaya, Kathryn Whitlock, John Ruzinski, Daniel Batlle, and Maryam Afkarian. "Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease." American Journal of Physiology-Renal Physiology 313, no. 2 (August 1, 2017): F487—F494. http://dx.doi.org/10.1152/ajprenal.00074.2017.
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The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13–20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P < 0.001). Enzymatic activities of ACE, ACE2, and APA were 6.2-, 3.2-, and 18.8-fold higher, respectively, in diabetic animals ( P < 0.001). Angiotensin II was 2.4-fold higher in diabetic animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 109 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy.
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Wakahara, Shigeyuki, Tadashi Konoshita, Shinichi Mizuno, Makoto Motomura, Chikako Aoyama, Yasukazu Makino, Norihiro Kato, Ichiro Koni, and Isamu Miyamori. "Synergistic Expression of Angiotensin-Converting Enzyme (ACE) and ACE2 in Human Renal Tissue and Confounding Effects of Hypertension on the ACE to ACE2 Ratio." Endocrinology 148, no. 5 (May 1, 2007): 2453–57. http://dx.doi.org/10.1210/en.2006-1287.
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Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.
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Li, Bing, Yan Hong Wang, Ju Mei Wang, and Wei De Shen. "Full Length cDNA Cloning and Expression Characteristics of Ace Gene from Wild Silkworm, Bombyx mandarina." Advanced Materials Research 175-176 (January 2011): 51–55. http://dx.doi.org/10.4028/www.scientific.net/amr.175-176.51.
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Acetylcholinesterase (AChE), which contains two subfamilies, ace1 and ace2 in insects, was identified to be the target of organophosphorous and carbamate insecticides. To research the sequences and tissues expressions of two aces, full length cDNAs encoding two ace genes were cloned, designated as Bmm-ace1 and Bmm-ace2 from larvae of the Bombyx mandarina. The amino acid sequence of Bmm-ace1 shared 99.71 % homology with its homolog, Bm-ace1, in silkworm, Bombyx mori, with two mutations (G664S and S307P), and the amino acid sequence of Bmm-ace2 shared 99.37 % homology with Bm-ace2, in B. mori , with four mutations (M18I, N233S, I310V and G621S). Tissue expression analysis showed that ace1 gene expressed only in the brains and fat bodies of B. mandarina, while ace2 genes expressed in all the tissues tested. ace1 and ace2 expressed highly in brains and fat bodies. The present results are significant to the study of resistance evolution of Lepidorptera as well as the understanding of the mechanism of pesticide resistance of insects.
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Wallace, Arthur W., Piera M. Cirillo, James C. Ryan, Nickilou Y. Krigbaum, Anusha Badathala, and Barbara A. Cohn. "Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study." BMJ Open 11, no. 12 (December 2021): e050051. http://dx.doi.org/10.1136/bmjopen-2021-050051.
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ObjectivesSARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.DesignThis is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.SettingMedical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2–1.7). Initiating (OR: 0.3; 95% CI 0.2–0.5) or continuous (OR: 0.6; 95% CI 0.5–0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.ConclusionsRecent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.
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Saleem, Muhammad. "Effect of Chemical Activating Agents on Surface Area and Methylene Blue Uptake Capacity of Activated Carbons." Pakistan Journal of Scientific & Industrial Research Series A: Physical Sciences 64, no. 3 (September 29, 2021): 254–64. http://dx.doi.org/10.52763/pjsir.phys.sci.64.3.2021.254.264.
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Activated carbon from Acacia asak (Fabaceae) tree branches was prepared utilizing three-steps- process and H3P04, ZnCl2, H2S04, K2C03, Na0H and K0H as chemical activating agents. In addition to the elemental analysis of precursor materials, produced activated carbon (ATB-AC) was also analyzed for moisture content, ash content, pH value, bulk density, volatile matter, hardness, specific surface area (SBET), iodine number and pore volume. Results revealed that the quality of ATB-AC is well comparable to the available commercial activated carbon (CAC). The SBET was found to be in the order of ATB-AC1> ATB- AC2> ATB-AC4> ATB-AC6> ATB-AC3> ATB-AC5. All the produced ATB-AC demonstrated good MB (methylene blue) removal efficiency, whereas ATB-AC1 and ATB-AC2 (produced from H3P04, and ZnCl2) showed higher efficiency. It is concluded that the chemical activating agent has significant effect on produced AC keeping all other production parameters constant. Among the six studied chemicals, H3P04 and ZnCl2 produced AC exhibited high SBET surface area and MB uptake capacity.
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Haghighi, Mahdi Montazer, Erfan Ghani Kakhki, Christine Sato, Mahdi Ghani, and Ekaterina Rogaeva. "The Intersection between COVID-19, the Gene Family of ACE2 and Alzheimer’s Disease." Neuroscience Insights 15 (January 2020): 263310552097574. http://dx.doi.org/10.1177/2633105520975743.
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We reviewed factors that might influence COVID-19 outcomes (eg, neurological symptoms), including the link to Alzheimer’s disease. Since the virus triggers COVID-19 infection through binding to ACE2, we focused on the ACE2 gene family, including ACE. Both ACE2 and ACE are involved in the renin–angiotensin system (RAS). In general, ACE causes inflammation and vasoconstriction, while ACE2 leads to anti-inflammation activity and vasodilation. The disturbed balance between these counter-regulatory pathways could influence susceptibility to COVID-19. Notably, dysregulation of the RAS-equilibrium contributes to Alzheimer’s disease. Differences in the incidence and symptoms of COVID-19 in diverse populations could be attributed to variability in the human genome. For example, ACE and ACE2 variations could modify the outcome of COVID-19 in different populations. It would be important to conduct genome-wide studies to detect variants influencing COVID-19 presentation, with a special focus on variants affecting immune-related pathways and expression of RAS-related genes.
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Fleming, Ingrid, Karin Kohlstedt, and Rudi Busse. "New fACEs to the Renin-Angiotensin System." Physiology 20, no. 2 (April 2005): 91–95. http://dx.doi.org/10.1152/physiol.00003.2005.
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Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Recent evidence suggests that some of the beneficial effects of ACE inhibitors can be attributed to the activation of a distinct ACE signaling cascade rather than to the changes in angiotensin II and bradykinin levels. Moreover, at least one other ACE homolog (ACE2) plays a significant role in the regulation of heart and kidney function.
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Chamata, Yara, Kim G. Jackson, Kimberly A. Watson, and Paula Jauregi. "Whey-Derived Peptides at the Heart of the COVID-19 Pandemic." International Journal of Molecular Sciences 22, no. 21 (October 28, 2021): 11662. http://dx.doi.org/10.3390/ijms222111662.
Full textAbstract:
The renin–angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed by employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.
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Xiao, Liang, Karla K. V. Haack, and Irving H. Zucker. "Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 signaling." American Journal of Physiology-Cell Physiology 304, no. 11 (June 1, 2013): C1073—C1079. http://dx.doi.org/10.1152/ajpcell.00364.2012.
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Brain ANG II plays an important role in modulating sympathetic function and homeostasis. The generation and degradation of ANG II are carried out, to a large extent, through the angiotensin-converting enzyme (ACE) and ACE2, respectively. In disease states, such as hypertension and chronic heart failure, central expression of ACE is upregulated and ACE2 is decreased in central sympathoregulatory neurons. In this study, we determined the expression of ACE and ACE2 in response to ANG II in a neuronal cell culture and the subsequent signaling mechanism(s) involved. A mouse catecholaminergic neuronal cell line (CATH.a) was treated with ANG II (30, 100, and 300 nM) for 24 h, and protein expression was determined by Western blot analysis. ANG II induced a significant dose-dependent increase in ACE and decrease in ACE2 mRNA and protein expression in CATH.a neurons. This effect was abolished by pretreatment of the cells with the p38 MAPK inhibitor SB-203580 (10 μM) 30 min before administration of ANG II or the ERK1/2 inhibitor U-0126 (10 μM). These data suggest that ANG II increases ACE and attenuates ACE2 expression in neurons via the ANG II type 1 receptor, p38 MAPK, and ERK1/2 signaling pathways.
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Hooper, Nigel M., Daniel W. Lambert, and Anthony J. Turner. "Discovery and characterization of ACE2 – a 20-year journey of surprises from vasopeptidase to COVID-19." Clinical Science 134, no. 18 (September 2020): 2489–501. http://dx.doi.org/10.1042/cs20200476.
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Abstract Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin–angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.
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Shaltout, Hossam A., Brian M. Westwood, David B. Averill, Carlos M. Ferrario, Jorge P. Figueroa, Debra I. Diz, James C. Rose, and Mark C. Chappell. "Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II." American Journal of Physiology-Renal Physiology 292, no. 1 (January 2007): F82—F91. http://dx.doi.org/10.1152/ajprenal.00139.2006.
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Despite the evidence that angiotensin-converting enzyme (ACE)2 is a component of the renin-angiotensin system (RAS), the influence of ACE2 on angiotensin metabolism within the kidney is not well known, particularly in experimental models other than rats or mice. Therefore, we investigated the metabolism of the angiotensins in isolated proximal tubules, urine, and serum from sheep. Radiolabeled [125I]ANG I was hydrolyzed primarily to ANG II and ANG-(1–7) by ACE and neprilysin, respectively, in sheep proximal tubules. The ACE2 product ANG-(1–9) from ANG I was not detected in the absence or presence of ACE and neprilysin inhibition. In contrast, the proximal tubules contained robust ACE2 activity that converted ANG II to ANG-(1–7). Immunoblots utilizing an NH2 terminal-directed ACE2 antibody revealed a single 120-kDa band in proximal tubule membranes. ANG-(1–7) was not a stable product in the tubule preparation and was rapidly hydrolyzed to ANG-(1–5) and ANG-(1–4) by ACE and neprilysin, respectively. Comparison of activities in the proximal tubules with nonsaturating concentrations of substrate revealed equivalent activities for ACE (ANG I to ANG II: 248 ± 17 fmol·mg−1·min−1) and ACE2 [ANG II to ANG-(1–7): 253 ± 11 fmol·mg−1·min−1], but lower neprilysin activity [ANG II to ANG-(1–4): 119 ± 24 fmol·mg−1·min−1; P < 0.05 vs. ACE or ACE2]. Urinary metabolism of ANG I and ANG II was similar to the proximal tubules; soluble ACE2 activity was also detectable in sheep serum. In conclusion, sheep tissues contain abundant ACE2 activity that converts ANG II to ANG-(1–7) but does not participate in the processing of ANG I into ANG-(1–9).
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Gill, Dipender, Marios Arvanitis, Paul Carter, Ana I. Hernández Cordero, Brian Jo, Ville Karhunen, Susanna C. Larsson, et al. "ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study." Royal Society Open Science 7, no. 11 (November 2020): 200958. http://dx.doi.org/10.1098/rsos.200958.
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Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium ( p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study ( p = 4 × 10 −4 ) and with circulating plasma ACE2 levels in the INTERVAL study ( p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study ( p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
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Kamilic, Jelena, Inge Hamming, A. Titia Lely, Ron Korstanje, Ute Schulze, Wilfred J. Poppinga, Anthony J. Turner, Nicola E. Clarke, Harry van Goor, and Gerjan J. Navis. "Rat Ace allele variation determines susceptibility to AngII-induced renal damage." Journal of the Renin-Angiotensin-Aldosterone System 12, no. 4 (July 25, 2011): 420–29. http://dx.doi.org/10.1177/1470320311415886.
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Introduction: Ace b/l polymorphism in rats is associated with differential tissue angiotensin-converting enzyme (ACE) expression and activity, and susceptibility to renal damage. Same polymorphism was recently found in outbred Wistar rat strain with b allele accounting for higher renal ACE, and provided a model for studying renin–angiotensin–aldosterone system (RAAS) response behind the innate high or low ACE conditions. Methods: We investigated the reaction of these alleles on chronic angiotensin II (AngII) infusion. Wistar rats were selected to breed male homozygotes for the b (WU-B) or l allele (WU-L) ( n = 12). For each allele, one group ( n = 6) received AngII infusion via an osmotic minipump (435 ng/kg/min) for 3 weeks. The other group ( n = 6) served as a control. Results: WU-B had higher ACE activity at baseline then WU-L. Interestingly, baseline renal ACE2 expression and activity were higher in WU-L. AngII infusion induced the same increase in blood pressure in both genotypes, no proteinuria, but caused tubulo-interstitial renal damage with increased α-SMA and monocyte/macrophage influx only in WU-B ( p < 0.05). Low ACE WU-L rats did not develop renal damage. Conclusion: AngII infusion causes proteinuria-independent renal damage only in rats with genetically predetermined high ACE while rats with low ACE seemed to be protected against the detrimental effect of AngII. Differences in renal ACE2, mirroring those in ACE, might be involved.
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Lubbe, Lizelle, Gyles E. Cozier, Delia Oosthuizen, K. Ravi Acharya, and Edward D. Sturrock. "ACE2 and ACE: structure-based insights into mechanism, regulation and receptor recognition by SARS-CoV." Clinical Science 134, no. 21 (November 2020): 2851–71. http://dx.doi.org/10.1042/cs20200899.
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Abstract Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin–angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer’s dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure–function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect–host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.
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Mizuiri, Sonoo. "ACE and ACE2 in kidney disease." World Journal of Nephrology 4, no. 1 (2015): 74. http://dx.doi.org/10.5527/wjn.v4.i1.74.
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Batlle, D., M. Jose Soler, and M. Ye. "ACE2 and Diabetes: ACE of ACEs?" Diabetes 59, no. 12 (November 29, 2010): 2994–96. http://dx.doi.org/10.2337/db10-1205.
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Thomas, M., and C. Tikellis. "ACE2; an ACE up the Sleeve?" Current Enzyme Inhibition 1, no. 1 (January 1, 2005): 51–63. http://dx.doi.org/10.2174/1573408052952739.
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Cuddy, Leah K., Dmitry Prokopenko, Eric P. Cunningham, Ross Brimberry, Peter Song, Rory Kirchner, Brad A. Chapman, et al. "Aβ-accelerated neurodegeneration caused by Alzheimer’s-associated ACE variant R1279Q is rescued by angiotensin system inhibition in mice." Science Translational Medicine 12, no. 563 (September 30, 2020): eaaz2541. http://dx.doi.org/10.1126/scitranslmed.aaz2541.
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Recent genome-wide association studies identified the angiotensin-converting enzyme gene (ACE) as an Alzheimer’s disease (AD) risk locus. However, the pathogenic mechanism by which ACE causes AD is unknown. Using whole-genome sequencing, we identified rare ACE coding variants in AD families and investigated one, ACE1 R1279Q, in knockin (KI) mice. Similar to AD, ACE1 was increased in neurons, but not microglia or astrocytes, of KI brains, which became elevated further with age. Angiotensin II (angII) and angII receptor AT1R signaling were also increased in KI brains. Autosomal dominant neurodegeneration and neuroinflammation occurred with aging in KI hippocampus, which were absent in the cortex and cerebellum. Female KI mice exhibited greater hippocampal electroencephalograph disruption and memory impairment compared to males. ACE variant effects were more pronounced in female KI mice, suggesting a mechanism for higher AD risk in women. Hippocampal neurodegeneration was completely rescued by treatment with brain-penetrant drugs that inhibit ACE1 and AT1R. Although ACE variant-induced neurodegeneration did not depend on β-amyloid (Aβ) pathology, amyloidosis in 5XFAD mice crossed to KI mice accelerated neurodegeneration and neuroinflammation, whereas Aβ deposition was unchanged. KI mice had normal blood pressure and cerebrovascular functions. Our findings strongly suggest that increased ACE1/angII signaling causes aging-dependent, Aβ-accelerated selective hippocampal neuron vulnerability and female susceptibility, hallmarks of AD that have hitherto been enigmatic. We conclude that repurposed brain-penetrant ACE inhibitors and AT1R blockers may protect against AD.
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Prieto, Minolfa C., Romer A. González-Villalobos, Fady T. Botros, Victoria L. Martin, Javier Pagán, Ryousuke Satou, Lucienne S. Lara, et al. "Reciprocal changes in renal ACE/ANG II and ACE2/ANG 1–7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats." American Journal of Physiology-Renal Physiology 300, no. 3 (March 2011): F749—F755. http://dx.doi.org/10.1152/ajprenal.00383.2009.
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Alterations in the balance between ANG II/ACE and ANG 1–7/ACE2 in ANG II-dependent hypertension could reduce the generation of ANG 1–7 and contribute further to increased intrarenal ANG II. Upregulation of collecting duct (CD) renin may lead to increased ANG II formation during ANG II-dependent hypertension, thus contributing to this imbalance. We measured ANG I, ANG II, and ANG 1–7 contents, angiotensin-converting enzyme (ACE) and ACE2 gene expression, and renin activity in the renal cortex and medulla in the clipped kidneys (CK) and nonclipped kidneys (NCK) of 2K1C rats. After 3 wk of unilateral renal clipping, systolic blood pressure and plasma renin activity increased in 2K1C rats ( n = 11) compared with sham rats ( n = 9). Renal medullary angiotensin peptide levels were increased in 2K1C rats [ANG I: (CK = 171 ± 4; NCK = 251 ± 8 vs. sham = 55 ± 3 pg/g protein; P < 0.05); ANG II: (CK = 558 ± 79; NCK = 328 ± 18 vs. sham = 94 ± 7 pg/g protein; P < 0.001)]; and ANG 1–7 levels decreased (CK = 18 ± 2; NCK = 19 ± 2 pg/g vs. sham = 63 ± 10 pg/g; P < 0.001). In renal medullas of both kidneys of 2K1C rats, ACE mRNA levels and activity increased but ACE2 decreased. In further studies, we compared renal ACE and ACE2 mRNA levels and their activities from chronic ANG II-infused ( n = 6) and sham-operated rats ( n = 5). Although the ACE mRNA levels did not differ between ANG II rats and sham rats, the ANG II rats exhibited greater ACE activity and reduced ACE2 mRNA levels and activity. Renal medullary renin activity was similar in the CK and NCK of 2K1C rats but higher compared with sham. Thus, the differential regulation of ACE and ACE2 along with the upregulation of CD renin in both the CK and NCK in 2K1C hypertensive rats indicates that they are independent of perfusion pressure and contribute to the altered content of intrarenal ANG II and ANG 1–7.
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Turner, Anthony J., Sarah R. Tipnis, Jodie L. Guy, Gillian I. Rice, and Nigel M. Hooper. "ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors." Canadian Journal of Physiology and Pharmacology 80, no. 4 (April 1, 2002): 346–53. http://dx.doi.org/10.1139/y02-021.
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A human zinc metalloprotease (termed ACEH or ACE2) with considerable homology to angiotensin- converting enzyme (ACE) (EC 3.4.15.1) has been identified and subsequently cloned and functionally expressed. The translated protein contains an N-terminal signal sequence, a single catalytic domain with zinc-binding motif (HEMGH), a transmembrane region, and a small C-terminal cytosolic domain. Unlike somatic ACE, ACEH functions as a carboxypeptidase when acting on angiotensin I and angiotensin II or other peptide substrates. ACEH may function in conjunction with ACE and neprilysin in novel pathways of angiotensin metabolism of physiological significance. In contrast with ACE, ACEH does not hydrolyse bradykinin and is not inhibited by typical ACE inhibitors. ACEH is unique among mammalian carboxypeptidases in containing an HEXXH zinc motif but, in this respect, resembles a bacterial enzyme, Thermus aquaticus (Taq) carboxypeptidase (EC 3.4.17.19). Collectrin, a developmentally regulated renal protein, is homologous with the C-terminal region of ACEH but has no similarity with ACE and no catalytic domain. Thus, the ACEH protein may have evolved as a chimera of a single ACE-like domain and a collectrin domain. The collectrin domain may regulate tissue response to injury whereas the catalytic domain is involved in peptide processing events.Key words: ACEH, ACE2, metalloprotease, collectrin, carboxypeptidase, angiotensin II.
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Zhang, Xiaoqing, Shuren Li, and Shaoqian Niu. "ACE2 and COVID-19 and the resulting ARDS." Postgraduate Medical Journal 96, no. 1137 (June 10, 2020): 403–7. http://dx.doi.org/10.1136/postgradmedj-2020-137935.
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This article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future. In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising. Trial registration number: NCT04287686.
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Tyrankiewicz, Urszula, Mariola Olkowicz, Tomasz Skórka, Magdalena Jablonska, Anna Orzylowska, Anna Bar, Michal Gonet, et al. "Activation pattern of ACE2/Ang-(1–7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice." Journal of Applied Physiology 124, no. 1 (January 1, 2018): 52–65. http://dx.doi.org/10.1152/japplphysiol.00571.2017.
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Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8–10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1–7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1–10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1–7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1–7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1–7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.
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Li, Ningjun, Joseph Zimpelmann, Keding Cheng, John A. Wilkins, and Kevin D. Burns. "The role of angiotensin converting enzyme 2 in the generation of angiotensin 1–7 by rat proximal tubules." American Journal of Physiology-Renal Physiology 288, no. 2 (February 2005): F353—F362. http://dx.doi.org/10.1152/ajprenal.00144.2004.
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ANG converting enzyme (ACE) 2 (ACE2) is a homologue of ACE, which is not blocked by conventional ACE inhibitors. ACE2 converts ANG 1–10 (ANG I) to ANG 1–9, which can be hydrolyzed by ACE to form the biologically active peptide ANG 1–7. ACE2 is expressed in the kidney, but its precise intrarenal localization is unclear, and the role of intrarenal ACE2 in the production of ANG 1–7 is unknown. The present studies determined the relative distribution of ACE2 in the rat kidney and defined its role in the generation of ANG 1–7 in proximal tubule. In microdissected rat nephron segments, semiquantitative RT-PCR revealed that ACE2 mRNA was widely expressed, with relatively high levels in proximal straight tubule (PST). Immunohistochemistry demonstrated ACE2 protein in tubular segments, glomeruli, and endothelial cells. Utilizing mass spectrometry, incubation of isolated PSTs with ANG I (10−6 M) led to generation of ANG 1–7 (sensitivity of detection > 1 × 10−9 M), accompanied by the formation of ANG 1–8 (ANG II) and ANG 1–9. The ACE2 inhibitor DX600 completely blocked ANG I-mediated generation of ANG 1–7. Incubation of PSTs with ANG 1–9 also led to generation of ANG 1–7, an effect blocked by the ACE inhibitor captopril or enalaprilat, but not by DX600. Incubation of PSTs with ANG II or luminal perfusion of ANG II did not result in detection of ANG 1–7. The results indicate that ACE2 is widely expressed in rat nephron segments and contributes to the production of ANG 1–7 from ANG I in PST. ANG II may not be a major substrate for ACE2 in isolated PST. The data suggest that ACE2-mediated production of ANG 1–7 represents an important component of the proximal tubular renin-ANG system.
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Bánhegyi, Viktor, Attila Enyedi, Gábor Áron Fülöp, Attila Oláh, Ivetta Mányiné Siket, Csongor Váradi, Klaudia Bottyán, et al. "Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion in the Serum, Lungs and Heart." Cells 10, no. 7 (July 6, 2021): 1708. http://dx.doi.org/10.3390/cells10071708.
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Objective: Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men. Methods: Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded. Results: A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ± 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II: 166 ± 143 ng/mL, n = 19, ID: 198 ± 113 ng/mL, n = 44 and DD: 258 ± 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II: 1423 ± 1276 ng/mg, ID: 1040 ± 712 ng/mg and DD: 930 ± 1273 ng/mg, p > 0.05) in the same patients (values are in median ± IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman’s p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman’s Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ± 1% and 53 ± 2%, respectively). Conclusion: Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.
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Marraffa Hudson, Maria. "Ace high or Ace low?" Child Care 7, no. 5 (May 2010): 34. http://dx.doi.org/10.12968/chca.2010.7.5.47549.
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Mohaghegh, Sadra, Parisa Motie, and Saeed Reza Motamedian. "Role of ACE2 polymorphism in COVID-19: impact of age." Clinical Chemistry and Laboratory Medicine (CCLM) 59, no. 10 (May 14, 2021): 1623–27. http://dx.doi.org/10.1515/cclm-2020-1877.
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Abstract More than 2 million people have died as a result of the COVID-19 outbreak. Angiotensin-converting enzyme 2 (ACE2) is a counter-regulatory enzyme that converts angiotensin-2 to Ang-(1–7) form in the renin-angiotensin system. Several studies have been analyzed the correlation between ACE2 and COVID-19. Indeed, ACE2/Ang (1–7) system protects the lung against acute respiratory distress syndrome by its anti-inflammatory/anti-oxidant function. However, SARS-Cov-2 can use ACE2 for host cell entry. Expression of ACE2 can be altered by several factors, including hypertension, diabetes and obesity, which also could increase the severity of COVID-19 infection. Besides, since androgens increase the expression of ACE-2, males are at higher risks of COVID-19 infection. Although reported statistics showed a significantly different infection risks of COVID-19 between adults and children, the reason behind the different responses is still unclear. This review proposes the effect of ACE polymorphism on the severity of SARS-COV-2 induced pneumonia. The previous meta-analysis regarding the effect of ACE polymorphism on the severity of pneumonia showed that polymorphism only affects the adult’s illness severity and not the children. Two recent meta-analyses examined the effect of ACE polymorphism on the prevalence and mortality rate of COVID-19 and reported contradicting results. Our opinion paper suggests that the effect of ACE polymorphism on the severity of COVID-19 depends on the patients age, same as of the pneumonia.
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Sabir, Jamal SM, Abdelfatteh El Omri, Imran Ali Khan, Babajan Banaganapalli, Nahid H. Hajrah, Houda Zrelli, Abdulkader M. Shaikh Omar, et al. "ACE insertion/deletion genetic polymorphism, serum ACE levels and high dietary salt intake influence the risk of obesity development among the Saudi adult population." Journal of the Renin-Angiotensin-Aldosterone System 20, no. 3 (July 2019): 147032031987094. http://dx.doi.org/10.1177/1470320319870945.
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Introduction: Angiotensin-converting enzyme ( ACE), which contributes to adipocyte growth, differentiation and function, has recently been linked with both salt metabolism and obesity development. Therefore, this study has aimed to investigate the putative relationship between ACE genetic polymorphism, serum ACE levels and salt consumption on the risk of developing obesity in the Saudi population. Materials and methods: ACE genotype status of 267 adult Saudi volunteers (124 obese and 143 non-obese) was correlated with their serum ACE activity and dietary salt intake amounts. Results: Obesity was more prevalent in deletion-deletion genotype individuals ( p<0.03), under dominant, co-dominant and monoallelic conditions ( p<0.04). Deletion allele corresponds to serum ACE activity in obese patients ( p<0.05). The amount of salt intake (<6 g/d) was significantly associated with obesity and particularly high in deletion-deletion and insertion-deletion genotype carriers ( p<0.001). STITCH analysis underlined interactions of the ACE protein with sodium molecule, REN, ACE2, KNG1 and AGTR1 in a biological network. Conclusions: Our findings suggest the positive association between ACE deletion genotype, serum ACE activity and sodium intake with risk of obesity development in the Saudi population.
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Grewal, Ekjot, Bayu Sutarjono, and Ibbad Mohammed. "Angioedema, ACE inhibitor and COVID-19." BMJ Case Reports 13, no. 9 (September 2020): e237888. http://dx.doi.org/10.1136/bcr-2020-237888.
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SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system. While presently it is advised that patients should continue to use ACE inhibitors or angiotensin receptor blockers, questions still remain as to whether adverse effects are potentiated by the virus. Here, we report a case of a 57-year-old man, unknowingly with COVID-19, who presented to the emergency department with tongue swelling, shortness of breath and difficulty in speaking following 4 months taking benazepril, an ACE inhibitor. Finally, we also describe possible pathways that exist for SARS-CoV-2 to interact with the mechanism behind angioedema.
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Burns, Kevin D., Yuliya Lytvyn, Farid H. Mahmud, Denis Daneman, Livia Deda, David B. Dunger, John Deanfield, et al. "The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes." American Journal of Physiology-Renal Physiology 312, no. 2 (February 1, 2017): F335—F342. http://dx.doi.org/10.1152/ajprenal.00438.2016.
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The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1) levels of urinary RAAS components and 2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC ( P < 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 ( P < 0.0001, P = 0.0003, P = 0.003, and P = 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen ( P < 0.0001) and ACE activity ( P = 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range.
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Marques, F. Z., K. G. Pringle, M. Markus, A. Conquest, J. J. Hirst, M. Sarris, T. Zakar, B. J. Morris, and E. R. Lumbers. "147. MOLECULAR CHARACTERIZATION OF RENIN - ANGIOTENSIN SYSTEM COMPONENTS IN HUMAN INTRAUTERINE TISSUES AND FETAL MEMBRANES FROM VAGINAL DELIVERY AND CAESAREAN SECTION." Reproduction, Fertility and Development 22, no. 9 (2010): 65. http://dx.doi.org/10.1071/srb10abs147.
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The expression of the (pro)renin receptor (ATP6AP2) in late gestational human tissues suggests that the prorenin-angiotensin system (RAS) might influence pregnancy outcome. Here w e characterized the RAS in term fetal membranes (amnion and chorion), decidua and placenta (n = 38) from women undergoing elective cesarean section (non-labouring) or following spontaneous delivery (after labour), and myometrium (n = 16) from elective or emergency cesarean (labouring) deliveries. RT-qPCR was used to quantify prorenin (REN), AGT, ACE, ACE2, AGTR1, AGTR2, ATP6AP2 and MAS1 mRNAs, and immunohistochemistry was used to localize prorenin, AGT, ACE, ACE2 and AGTR1 proteins. In myometrium, mRNAs for downstream signalling proteins (ZBTB16, TGFB1 and PTGS2) were also measured. ACE and AGT mRNA levels were higher in labouring myometrium (P < 0.05), consistent with elevated production of angiotensin II (Ang II), which, by the upregulation of PTGS2 occurring in labour (P = 0.022), could influence labour. In amnion, expression of all RAS component mRNAs, except ATP6AP2, was low. After labour amnion showed lower ACE (P = 0.014) and higher AGTR2 (P = 0.01) mRNA levels. In decidua, RAS components other than AGTR1 and AGTR2 were abundant. Amnion and chorion exhibited higher immunostaining of AGT and prorenin than expected from their low mRNA levels, suggesting that these proteins could have been originated from decidua, where the cognate genes are more active. In placenta, prorenin and AGT were localized to syncytiotrophoblasts and ACE was localized to fetal capillary endothelial cells, while ACE2 distribution was diffuse. AGTR1 mRNA and protein expression was high in the placenta. We propose that ACE in fetal vessels could contribute Ang II to the fetus, while ACE2 in syncytiotrophoblasts might convert placental or maternal circulating Ang II to angiotensin-(1–7), which might then be supplied to the maternal bloodstream. In conclusion, the abundance and distribution of intrauterine RAS components suggest diverse roles for this local RAS in pregnancy.
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Cherney, David Z. I., Fengxia Xiao, Joseph Zimpelmann, Ronnie L. H. Har, Vesta Lai, James W. Scholey, Heather N. Reich, and Kevin D. Burns. "Urinary ACE2 in healthy adults and patients with uncomplicated type 1 diabetes." Canadian Journal of Physiology and Pharmacology 92, no. 8 (August 2014): 703–6. http://dx.doi.org/10.1139/cjpp-2014-0065.
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Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be renoprotective. We determined whether urinary ACE2 enzyme activity and protein levels (ELISA), as well as angiotensinogen and ACE, are elevated during clamped euglycemia (4–6 mmol·L–1) in patients with uncomplicated type 1 diabetes (T1D, n = 58) compared with normoglycemic controls (n = 21). We also measured the effect of clamped hyperglycemia (9–11 mmol·L–1) on each urinary factor in T1D patients. Urinary ACE2 activity and protein levels were higher during clamped euglycemia in T1D compared with the controls (p < 0.0001). In contrast, urinary angiotensinogen levels (p = 0.27) and ACE excretion (p = 0.68) did not differ. In response to clamped hyperglycemia in T1D, urinary ACE2 protein decreased (p < 0.0001), whereas urinary ACE2 activity as well as angiotensinogen and ACE levels remained unchanged. Urinary ACE2 activity and protein expression are increased in T1D patients prior to the onset of clinical complications. Further work is required to determine the functional role of urinary ACE2 in early T1D.