Journal articles: 'Angiopoietin'

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CHANG, Hang, Bao-Wei WANG, Peiliang KUAN, and Kou-Gi SHYU. "Cyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells." Clinical Science 104, no. 4 (March 20, 2003): 421–28. http://dx.doi.org/10.1042/cs1040421.

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Endothelial cells are essential for neovascularization. Angiopoietins and Tie receptors are required for a normal vasculature. How cyclical mechanical stretch affects the expression of components of the angiopoietin system is not known. In this study, we investigated the regulation of angiopoietins and Tie receptors by cyclical mechanical stretch in cultured human umbilical vein endothelial cells (HUVECs). HUVECs grown on a flexible membrane base were stretched by vacuum to 20% elongation, at 60cycles/min. The levels of angiopoietin-2 protein began to increase as early as 2h after stretch was initially applied, reached a maximum of 2.7-fold over the control value by 6h. The Tie2 receptor protein showed the same pattern as Ang-2. These increases in angiopoietin-2 and Tie2 receptor proteins at 6h were blocked by the addition (30min before stretch) of the protein kinase C inhibitor Gö6976 (16nM) or the tyrosine kinase inhibitor herbimycin A (24µM). Similar to protein expression, the levels of angiopoietin-2 and Tie2 receptor mRNAs in HUVECs increased 3.1-fold and 2.5-fold respectively after stretch for 6h. These increases were also blocked by Gö6976 or herbimycin A. Cyclical mechanical stretch increased (and Gö6976 or herbimycin A abrogated these increases) the immunohistochemical labelling of angiopoietin-2 and Tie2 receptor after a 6h stretch. The levels of angiopoietin-1 and Tie1 receptor proteins, mRNAs and immunohistochemical staining were unaffected by cyclical mechanical stretch. Thus cyclical mechanical stretch activates the expression of angiopoietin-2 and the Tie2 receptor, but not angiopoietin-1 or the Tie1 receptor, in cultured HUVECs. This mechanical effect is probably mediated by the tyrosine kinase and protein kinase C pathways.

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Tsakogiannis, Dimitris, Asimina Nikolakopoulou, Flora Zagouri, Grigorios Stratakos, Konstantinos Syrigos, Eleni Zografos, Nikolaos Koulouris, and Garyfalia Bletsa. "Update Overview of the Role of Angiopoietins in Lung Cancer." Medicina 57, no. 11 (November 1, 2021): 1191. http://dx.doi.org/10.3390/medicina57111191.

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Angiogenesis is a biological process that involves the formation of new blood vessels from the existing vasculature, and it plays a fundamental role in the development and progression of several types of cancer, including lung cancer. The angiopoietin/Tie2 ligand/receptor system orchestrates vascular integrity. In particular, Angiopoietin-1 activates the endothelial cell (EC)-specific receptor tyrosine kinase,Tie2,which is essential for preserving endothelial quiescence. On the other hand, Angiopoietin-2 acts as an inhibitor of the Angiopoietin-1/Tie2 signaling pathways, thus facilitating the destabilization of quiescent endothelium in cases of inflammation and cancer. Clinical studies have proven that high levels of Angiopoietin-2 indicate the development of non-small-cell lung carcinomas (NSCLC), while high levels of Angiopoietin-2 are strongly related to tumor angiogenesis, lymphangiogenesis, metastasis, and poor prognosis. Interestingly, the association of Angiopoietin-2 levels with the type of surgical approach makes Angiopoietin-2 a valuable factor in selecting the most suitable therapeutic strategy for lung cancer patients. The role of the Angiopoietin-1 and Angiopoietin-4 levels in NSCLC development requires further investigation. The present review focuses on the clinical impact of the Angiopoietin-1, Angiopoietin-2, and Angiopoietin-4 levels in patients diagnosed with NSCLC, emphasizing the interaction between them, and how they affect the development, progression, and metastasis of lung disease. Finally, it estimates the role of angiopoietins levels in the effective therapy of lung cancer patients.

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Sabatino, Laura, Claudia Kusmic, Giuseppina Nicolini, Rosario Amato, Giovanni Casini, Giorgio Iervasi, and Silvana Balzan. "T3 enhances Ang2 in rat aorta in myocardial I/R: comparison with left ventricle." Journal of Molecular Endocrinology 57, no. 3 (October 2016): 139–49. http://dx.doi.org/10.1530/jme-16-0118.

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Angiogenesis is important for recovery after tissue damage in myocardial ischemia/reperfusion, and tri-iodothyronine (T3) has documented effects on angiogenesis. The angiopoietins 1/2 and tyrosine kinase receptor represent an essential system in angiogenesis controlling endothelial cell survival and vascular maturation. Recently, in a 3-day ischemia/reperfusion rat model, the infusion of a low dose of T3 improved the post-ischemic recovery of cardiac function. Adopting this model, our study aimed to investigate the effects of T3 on the capillary index and the expression of angiogenic genes as the angiopoietins 1/2 and tyrosine kinase receptor system, in the thoracic aorta and in the left ventricle. In the thoracic aorta, T3 infusion significantly improved the angiogenic sprouting and angiopoietin 2 expression. Instead, Sham-T3 group did not show any significant increment of capillary density and angiopoietin 2 expression. In the area at risk (AAR) of the left ventricle, T3 infusion did not increase capillary density but restored levels of angiopoietin 1, which were reduced in I/R group. Angiopoietin 2 levels were similar to Sham group and unchanged by T3 administration. In the remote zone, T3 induced a significant increment of both angiopoietin 1/2. In conclusion, T3 infusion induced a different response of angiopoietin 1/2 between the ventricle (the AAR and the remote zone) and the thoracic aorta, probably reflecting the different action of angiopoietin 1/2 in cardiomyocytes and endothelial cells. Overall, these data suggest a new aspect of T3-mediated cardioprotection through angiogenesis.

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Khan, Aafaque Ahmad, Varot K. Sandhya, Priyata Singh, Deepak Parthasarathy, Awinav Kumar, Jayshree Advani, Rudrappa Gattu, et al. "Signaling Network Map of Endothelial TEK Tyrosine Kinase." Journal of Signal Transduction 2014 (October 13, 2014): 1–6. http://dx.doi.org/10.1155/2014/173026.

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TEK tyrosine kinase is primarily expressed on endothelial cells and is most commonly referred to as TIE2. TIE2 is a receptor tyrosine kinase modulated by its ligands, angiopoietins, to regulate the development and remodeling of vascular system. It is also one of the critical pathways associated with tumor angiogenesis and familial venous malformations. Apart from the vascular system, TIE2 signaling is also associated with postnatal hematopoiesis. Despite the involvement of TIE2-angiopoietin system in several diseases, the downstream molecular events of TIE2-angiopoietin signaling are not reported in any pathway repository. Therefore, carrying out a detailed review of published literature, we have documented molecular signaling events mediated by TIE2 in response to angiopoietins and developed a network map of TIE2 signaling. The pathway information is freely available to the scientific community through NetPath, a manually curated resource of signaling pathways. We hope that this pathway resource will provide an in-depth view of TIE2-angiopoietin signaling and will lead to identification of potential therapeutic targets for TIE2-angiopoietin associated disorders.

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Abdulmalek, Kefeya, Fathia Ashur, Nadine Ezer, Fengchun Ye, Sheldon Magder, and Sabah N. A. Hussain. "Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 281, no. 3 (September 1, 2001): L582—L590. http://dx.doi.org/10.1152/ajplung.2001.281.3.l582.

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In this study, we assessed the effects of in vivo hypoxia on the expression of Tie-2 receptors and angiopoietins in various organs of conscious rats and correlated these effects with the expression of hypoxia-inducible factor-1 (HIF-1). RT-PCR and Southern blotting were used to amplify mRNA expression of angiopoietin-1, -2, and -3, Tie-2, and HIF-1α in tissues of normoxic and hypoxic (fraction of inspired oxygen of 9–10% for either 12 or 48 h) rats. Hypoxia provoked a decline in angiopoietin-1 mRNA and Tie-2 mRNA, protein, and phosphorylation levels in the lung, liver, cerebellum, and heart but not in the kidney and diaphragm. In comparison, hypoxia raised the levels of angiopoietin-2 mRNA in the cerebellum and angiopoietin-3 mRNA in the lung, kidney, and diaphragm. HIF-1α mRNA was abundant in most organs of normoxic rats but was significantly induced in the kidney and diaphragm of hypoxic rats. We conclude that in vivo hypoxia exerts inhibitory effects on the activity of the angiopoietin-1/Tie-2 receptor pathway through reduction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be mediated through the HIF-1 transcription factor.

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Hildbrand, Patrick, Vincenzo Cirulli, Robyn C. Prinsen, Kent A. Smith, Bruce E. Torbett, Daniel R. Salomon, and Laura Crisa. "The role of angiopoietins in the development of endothelial cells from cord blood CD34+ progenitors." Blood 104, no. 7 (October 1, 2004): 2010–19. http://dx.doi.org/10.1182/blood-2003-12-4219.

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Abstract Circulating endothelial progenitors contribute to neovascularization at sites of injury and tumorigenesis in postnatal life. Yet, the molecular mechanisms initiating the endothelial developmental program of these precursors remain elusive. Here we provide evidence that endothelial development from progenitors circulating in human cord blood requires angiopoietins, a set of growth factors also involved in vascular branching during embryogenesis. We show that cord blood cells with the potential for endothelial development reside in a CD34+CD11b+ subset capable of autonomously producing and binding angiopoietins. Functionally, endogenous angiopoietin-1 regulates initial endothelial cell commitment, whereas angiopoietin-2 enhances expansion of the endothelial cell progeny. These findings suggest a role for angiopoietins as regulators of endothelial development from circulating progenitors and imply a function of angiopoietins at distinct developmental steps in postnatal angiogenesis.

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Morisada, Tohru, Yoshiaki Kubota, Takashi Urano, Toshio Suda, and Yuichi Oike. "Angiopoietins and Angiopoietin-Like Proteins in Angiogenesis." Endothelium 13, no. 2 (January 2006): 71–79. http://dx.doi.org/10.1080/10623320600697989.

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Cordeiro, Ana Lúcia, António Figueiredo, Inês Tomada, Henrique de Almeida, and Delminda Neves. "Characterization of the Expression of Ang1, Ang2, and Tie2 in the Corpus Cavernosum of the Rat during Aging." Microscopy and Microanalysis 16, no. 6 (October 25, 2010): 699–709. http://dx.doi.org/10.1017/s1431927610094006.

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AbstractAging is the single most significant risk factor for erectile dysfunction (ED), leading to structural modification of cavernous tissue and altering expression of vascular growth factors. The angiopoietin/Tie2 system has been recently considered as a potential target for therapy of vascular disorders, including ED. Hence, the aim of this study was to analyze expression of angiopoietin1 (Ang1), angiopoietin2 (Ang2), and their receptor Tie2 in corpus cavernosum (CC) of rat during aging (6, 12, 18, and 24 months). The expression of Ang1, Ang2, and Tie2 was studied by immunohistochemistry and immunofluorescence, followed by semiquantification after Western blotting. Both Ang1 and Ang2 were localized mainly in perivascular smooth muscle and endothelial cells, while Tie2 was strictly detected at the vascular endothelium. A significant decrease in Ang2's expression was observed at 12 months when compared with 6-month-old rats, a tendency that reverses in older animals. No significant differences were demonstrated for Ang1 or Tie2, which is consistent with their constitutive expression in CC. The ratios Ang1/Tie2 and Ang2/Tie2 were also calculated and both decrease during aging, while no marked variation was observed for Ang1/Ang2. Our results suggest that the angiopoietin/Tie2 system participate in the vascular maintenance and remodeling of the CC during aging.

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Person, Anthony, Wendy Xiong, Christian Erickson, Kate Shields, Jun Li, Ming BI, Guoping Wu, and Vassili Kalabokis. "Angiopoietins and angiopoietin-like proteins bind to LILRA/B receptors and activate innate immune responses in human monocytes (INC1P.405)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 54.26. http://dx.doi.org/10.4049/jimmunol.194.supp.54.26.

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Abstract Angiopoietins and Angiopoietin-like (ANGPTL) proteins are secreted glycoproteins that play multiple roles in angiogenesis, lipid metabolism, hematopoietic stem cell expansion, and inflammation. Unlike Angiopoietins, which are known to signal through the tyrosine kinase Tie1 or Tie2 receptors, ANGPTL proteins have long been considered orphan ligands. Recently, ANGPTL1, 2, 5, and 7 were shown to bind to human leukocyte immunoglobulin like receptor B2 (LILRB2), resulting in enhancement of human haematopoietic stem cell proliferation and expansion. Leukocyte immunoglobulin-like receptors (LILRs) also named ILTs, LIRs and CD85s, are a family of immunomodulatory molecules that are expressed on professional APCs and regulate their functional properties to influence immune activation and inhibition. While the MHC class I complexes have been identified as the physiological ligands for many LILR members, the direct interaction between LILRs and ANGPTLs has suggested a new signaling mechanism for those two groups of molecules. We have tested Angiopoietins and ANGPTL proteins in binding studies with the LILRA and LILRB family members, and identified additional LILR family members as potential receptors of Angiopoietin-1 and several ANGPTL proteins. We find correlations between these newly described interactions of Angiopoietins and ANGPTL proteins with LILR family members and their abilities to activate innate immune responses in human monocytes.

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Blecharz, Kinga G., Dietmar Frey, Tobias Schenkel, Vincent Prinz, Gloria Bedini, Susanne M. Krug, Marcus Czabanka, et al. "Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease." Journal of Cerebral Blood Flow & Metabolism 37, no. 4 (July 21, 2016): 1527–39. http://dx.doi.org/10.1177/0271678x16658301.

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Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future.

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Duits, Ashley J., and John B. Schnog. "Vascular Growth Factors in Patients with Sickle Cell Disease." Blood 106, no. 11 (November 16, 2005): 3787. http://dx.doi.org/10.1182/blood.v106.11.3787.3787.

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Abstract Angiogenesis plays a central role in neovascular processes. In sickle cell patients neovascularization is considered a common feature that is associated with complications such as retinopathy and cerebrovascular disease. Several studies have reported increased vascular growth factor levels such as vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in small groups of patients. Recently the angiopoietin/Tie2 system has been shown to be of major importance in vessel maturation. In order to thoroughly characterize vascular growth factor profiles in sickle cell patients we analyzed serum levels of VEGF, PlGF, Angiopoietin-1, Angiopoietin-2, Tie-2 and erythropoietin (EPO) during the asymptomatic phase as well as during painful crises in HbSS patients (n=42) and compared these to levels in HbAA controls (n=30). Also, levels were compared between patients with and without a history of acute vaso-occlusive complications the year prior to sample collection. Serum Angiopoietin-2, Tie-2 and EPO levels were significantly higher in sickle cell patients as compared to controls (p<0.01, p=0.03 and p<0.01 respectively), whereas PlGF and VEGF serum levels were similar between patients and controls (p= 0.21 and p=0.5). Only Angiopoietin-2 and EPO serum levels were significantly increased in sickle cell patients during acute vaso-occlusive crises as compared to levels in asymptomatic patients (p<0.01 and p=0.03 respectively). No differences were detected in measured parameters between patients with a history of acute vaso-occlusive complications as compared to patients without acute vaso-occlusive complications in the preceding year. Our results show a specific pattern of angiopoietins in sickle cell patients. Considering the importance of endothelial cell activation in sickle cell disease and the regulation of endothelial cell survival and blood vessel maturation by the angiopoietin/Tie-2 system, further analysis of angiogenesis in sickle cell disease is warranted.

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Singh, Puspendra P., Sneha Bhandari, Ravendra K. Sharma, Neeru Singh, and Praveen K. Bharti. "Association of Angiopoietin Dysregulation in Placental Malaria with Adverse Birth Outcomes." Disease Markers 2020 (January 13, 2020): 1–8. http://dx.doi.org/10.1155/2020/6163487.

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Malaria in pregnancy causes adverse birth outcomes due to sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Angiopoietins are critical regulators of vascular development and formation of placental villous vasculature. Angiopoietin-1 and Angiopoietin-2 concentrations were measured in peripheral and placental plasma samples from 70 malaria-infected and 216 control women using commercially available DuoSet ELISA development kit. Angiopoietins increased in placental plasma (ANG1-5833.5 pg/ml and ANG2-9580.6 pg/ml) as compared to peripheral plasma (ANG1-2293.1 pg/ml and ANG2-1198.9 pg/ml, p<0.0001). The concentration of placental and peripheral ANG1 (6099.23 pg/ml and 2320.5 pg/ml) was significantly lower (5013.5 pg/ml, 2208.5 pg/ml), and ANG2 (9553.3 pg/ml, 1180.92 pg/ml) was significantly higher (9664.6 pg/ml, 1254.4 pg/ml) in malaria-positive cases as compared to malaria-negative (p<0.0001). The association of dysregulated angiopoietins in malaria with adverse birth outcomes showed that the peripheral and placental ANG1 concentration was lower and ANG2 concentration was higher in low-birth-weight baby and stillbirth birth outcome as compared to normal deliveries among malaria-positive group. Therefore, ANG1 and ANG2 could be considered a biomarker for adverse outcome during malaria in pregnancy.

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Yamakawa, Midori, Louis X. Liu, Adam J. Belanger, Taro Date, Takayuki Kuriyama, Mark A. Goldberg, Seng H. Cheng, Richard J. Gregory, and Canwen Jiang. "Expression of angiopoietins in renal epithelial and clear cell carcinoma cells: regulation by hypoxia and participation in angiogenesis." American Journal of Physiology-Renal Physiology 287, no. 4 (October 2004): F649—F657. http://dx.doi.org/10.1152/ajprenal.00028.2004.

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The hereditary von Hippel-Lindau (VHL) syndrome predisposes sufferers to highly vascularized tumors such as renal clear cell carcinoma (RCC) and central nervous system hemangioblastoma. In RCC4 and RCC786–0 VHL− cells with VHL mutations, the protein of hypoxia-inducible factor-1α (HIF-1α) is constitutively stabilized and the mRNA levels of HIF target genes, including vascular endothelial growth factor (VEGF), are elevated. However, the expression of angiopoietins in these cells and their involvement in angiogenesis are not well known. In this study, we compared the mRNA levels of angiopoietins in human kidney proximal tubule epithelial (RPTE) and RCC4 and RCC786–0 VHL− cells. In RPTE cells, angiopoietin-4 (Ang-4) expression was selectively induced by hypoxia or by expression of a hybrid form of HIF-1α. Under normoxic conditions, the mRNA levels of Ang-4 were higher in RCC4 and RCC786–0 VHL− than RPTE cells. Angiopoietin-1 expression was detectable in RCC4 and RCC786–0 VHL− cells but not RPTE cells. In RCC786–0 VHL+ cells, which were stably transfected with a wild-type copy of VHL, the mRNA levels of VEGF and Ang-4 were suppressed and the hypoxic response was restored. We also demonstrated that stimulation of endothelial tube formation by conditioned medium harvested from RCC4 cells was inhibited by a soluble Tie-2 receptor. These results suggest that the angiopoietin/Tie-2 system may participate in the angiogenic response to hypoxia in renal tissues and in tumor angiogenesis in renal carcinoma.

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SHYU, Kou-Gi, Chih-Chuan CHANG, Bao-Wei WANG, Peiliang KUAN, and Hang CHANG. "Increased expression of angiopoietin-2 and Tie2 receptor in a rat model of myocardial ischaemia/reperfusion." Clinical Science 105, no. 3 (September 1, 2003): 287–94. http://dx.doi.org/10.1042/cs20030025.

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The angiopoietins and Tie receptors are involved in blood vessel formation. The role of the angiopoietin/Tie receptor system in myocardial ischaemia/reperfusion is not well known. To investigate the participation of angiopoietins and Tie receptors in myocardial ischaemia/reperfusion, adult Wistar rats were studied in which the left coronary artery was ligated for 30 min, followed by reperfusion. Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie1 and Tie2 were measured immediately after relief of occlusion, and 1, 6, 24 and 72 h after reperfusion, by Northern blot, Western blot and immunohistochemical staining. Ang2 mRNA was increased significantly at 24 h and 48 h after reperfusion, and returned to baseline levels at 72 h, in the jeopardized myocardium. Tie2 mRNA increased 3.4-fold immediately after the relief of occlusion, reached a maximum 8-fold increase at 24 h after reperfusion and remained elevated up to 72 h. Ang2 protein levels also increased after reperfusion, reaching a maximum 2.2-fold increase at 48 h after reperfusion. Tie2 protein increased immediately after relief of ischaemia, and showed a significant increase from 6 h to 72 h after reperfusion as compared with the sham control. Ang1 and Tie1 mRNA and protein did not show significant changes after ischaemia/reperfusion. Immunohistochemical studies also showed increased immunoreactivity of Ang2 and Tie2 in the jeopardized myocardium after ischaemia/reperfusion. In conclusion, expression of both Ang2 and Tie2 increased after ischaemia/reperfusion in the rat ventricular myocardium, while the expression of Ang1 and Tie1 did not.

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Akwii, Racheal G., Md S. Sajib, Fatema T. Zahra, and Constantinos M. Mikelis. "Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology." Cells 8, no. 5 (May 17, 2019): 471. http://dx.doi.org/10.3390/cells8050471.

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Angiopoietins 1–4 (Ang1–4) represent an important family of growth factors, whose activities are mediated through the tyrosine kinase receptors, Tie1 and Tie2. The best characterized are angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2). Ang1 is a potent angiogenic growth factor signaling through Tie2, whereas Ang2 was initially identified as a vascular disruptive agent with antagonistic activity through the same receptor. Recent data demonstrates that Ang2 has context-dependent agonist activities. Ang2 plays important roles in physiological processes and the deregulation of its expression is characteristic of several diseases. In this review, we summarize the activity of Ang2 on blood and lymphatic endothelial cells, its significance in human physiology and disease, and provide a current view of the molecular signaling pathways regulated by Ang2 in endothelial cells.

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Oike, Yuichi, Kunio Yasunaga, and Toshio Suda. "Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis." International Journal of Hematology 80, no. 1 (July 1, 2004): 21–28. http://dx.doi.org/10.1532/ijh97.04034.

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Zadeh, Gelareh, Keyvan Koushan, Qian Baoping, Patrick Shannon, and Abhijit Guha. "Role of Angiopoietin-2 in Regulating Growth and Vascularity of Astrocytomas." Journal of Oncology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/659231.

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Angiopoietins and Tie2 are angiogenic-specific ligand and receptor complex that have been shown to play a critical role in tumor angiogenesis. Angiopoietin-2 (Ang2) is one of four ligands for receptor Tie2 and it is the naturally occurring antagonist to Tie2, inhibiting the action of Angiopoietin-1 (Ang1). Over the last decade, significant research has focused on elucidating the role of Ang2 in cancer biology and its exact role in tumor angiogenesis remains elusive. In this study we have focused on establishing the role of Ang2 in angiogenesis of malignant astrocytomas. We have demonstrated that Ang2 significantly enhances the vascular growth of malignant astrocytomas and constant upregulation of Ang2 throughout all phases of tumor growth generates abnormal vascular structures that are not typically seen in human astrocytomas, suggesting that Ang2 plays a tumor stage-dependent role and is not a consistently elevated throughout all growth stages of malignant astroctyomas.

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David, S., and P. Kümpers. "Angiopoietin 2." Der Nephrologe 4, no. 3 (May 2009): 266–68. http://dx.doi.org/10.1007/s11560-009-0285-9.

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Lee, Hyuek Jong, Chung-Hyun Cho, Su-Jeong Hwang, Han-Ho Choi, Kyung-Tae Kim, So Young Ahn, Ju-Hyun Kim, Jong-Lark Oh, Gyun Min Lee, and Gou Young Koh. "Biological characterization of angiopoietin‐3 and angiopoietin‐4." FASEB Journal 18, no. 11 (August 2004): 1200–1208. http://dx.doi.org/10.1096/fj.03-1466com.

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Saharinen, Pipsa, Katja Kerkelä, Niklas Ekman, Marie Marron, Nicholas Brindle, Gyun Min Lee, Hellmut Augustin, Gou Young Koh, and Kari Alitalo. "Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2." Journal of Cell Biology 169, no. 2 (April 25, 2005): 239–43. http://dx.doi.org/10.1083/jcb.200411105.

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The Tie1 receptor tyrosine kinase was isolated over a decade ago, but so far no ligand has been found to activate this receptor. Here, we have examined the potential of angiopoietins, ligands for the related Tie2 receptor, to mediate Tie1 activation. We show that a soluble Ang1 chimeric protein, COMP-Ang1, stimulates Tie1 phosphorylation in endothelial cells with similar kinetics and angiopoietin dose dependence when compared with Tie2. The phosphorylation of overexpressed Tie1 was weakly induced by COMP-Ang1 also in transfected cells that do not express Tie2. When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner. Tie1 phosphorylation was also induced by native Ang1 and Ang4, although less efficiently than with COMP-Ang1. In conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin proteins and that the activation is amplified via Tie2. These results should be important in dissecting the signal transduction pathways and biological functions of Tie1.

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Ward, E. G., K. Grosios, A. F. Markham, and P. F. Jones. "Genomic structures of the human angiopoietins show polymorphism in angiopoietin-2." Cytogenetic and Genome Research 94, no. 3-4 (2001): 147–54. http://dx.doi.org/10.1159/000048807.

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Mofarrahi, Mahroo, Thamir Nouh, Salman Qureshi, Loic Guillot, Dominique Mayaki, and Sabah N. A. Hussain. "Regulation of angiopoietin expression by bacterial lipopolysaccharide." American Journal of Physiology-Lung Cellular and Molecular Physiology 294, no. 5 (May 2008): L955—L963. http://dx.doi.org/10.1152/ajplung.00449.2007.

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Angiopoietins are ligands for Tie-2 receptors and play important roles in angiogenesis and inflammation. While angiopoietin-1 (Ang-1) inhibits inflammatory responses, angiopoietin-2 (Ang-2) promotes cytokine production and vascular leakage. In this study, we evaluated in vivo and in vitro effects of Escherichia coli lipopolysaccharides (LPS) on angiopoietin expression. Wild-type C57/BL6 mice were injected with saline (control) or E. coli LPS (20 mg/ml ip) and killed 6, 12, and 24 h later. The diaphragm, lung, and liver were excised and assayed for mRNA and protein expression of Ang-1, Ang-2, and Tie-2 protein and tyrosine phosphorylation. LPS injection elicited a severalfold rise in Ang-2 mRNA and protein levels in the three organs. By comparison, both Ang-1 and Tie-2 levels in the diaphragm, liver, and lung were significantly attenuated by LPS administration. In addition, Tie-2 tyrosine phosphorylation in the lung was significantly reduced in response to LPS injection. In vitro exposure to E. coli LPS elicited cell-specific changes in Ang-1 expression, with significant induction in Ang-1 expression being observed in cultured human epithelial cells, whereas significant attenuation of Ang-1 expression was observed in response to E. coli LPS exposure in primary human skeletal myoblasts. In both cell types, E. coli LPS elicited substantial induction of Ang-2 mRNA, a response that was mediated in part through NF-κB. We conclude that in vivo endotoxemia triggers functional inhibition of the Ang-1/Tie-2 receptor pathway by reducing Ang-1 and Tie-2 expression and inducing Ang-2 levels and that this response may contribute to enhanced vascular leakage in sepsis.

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Chong, Aun Yeong, Graham J. Caine, Bethan Freestone, Andrew D. Blann, and Gregory Y. H. Lip. "Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure." Journal of the American College of Cardiology 43, no. 3 (February 2004): 423–28. http://dx.doi.org/10.1016/j.jacc.2003.08.042.

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Bolin, M., E. Wiberg-Itzel, A. K. Wikstrom, M. Goop, A. Larsson, M. Olovsson, and H. Akerud. "Angiopoietin-1/Angiopoietin-2 Ratio for Prediction of Preeclampsia." American Journal of Hypertension 22, no. 8 (August 1, 2009): 891–95. http://dx.doi.org/10.1038/ajh.2009.97.

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Nishimura, Motoi, Takashi Miki, Rei Yashima, Norihide Yokoi, Hideki Yano, Yasufumi Sato, and Susumu Seino. "Angiopoietin-3, a novel member of the angiopoietin family." FEBS Letters 448, no. 2-3 (April 9, 1999): 254–56. http://dx.doi.org/10.1016/s0014-5793(99)00381-6.

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Dungan, J. S. "Angiopoietin-1/Angiopoietin-2 Ratio for Prediction of Preeclampsia." Yearbook of Obstetrics, Gynecology and Women's Health 2010 (January 2010): 133–34. http://dx.doi.org/10.1016/s1090-798x(10)79326-7.

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Hess, A. P., J. Hirchenhain, A. Schanz, S. Talbi, A. E. Hamilton, L. C. Giudice, and J. S. Krüssel. "Angiopoietin-1 and -2 mRNA and protein expression in mouse preimplantation embryos and uteri suggests a role in angiogenesis during implantation." Reproduction, Fertility and Development 18, no. 5 (2006): 509. http://dx.doi.org/10.1071/rd05110.

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After attachment and migration through the endometrial epithelium, the embryo must induce angiogenesis within the endometrial stroma to successfully complete the implantation process. Growth factors have been shown to play an important role in embryo implantation and placentation. The aim of the study was to investigate the expression of angiopoietin-1 and -2 (Ang-1 and -2) mRNA and protein expression during the development of single preimplantation mouse embryos and of possible complementary expression in mouse uteri. Angiopoietin-1 mRNA was expressed throughout development in 78% of zygotes, 66% of 2-cell-embryos, 71% of 4-cell-embryos, 70% of 8-cell-embryos, 60% of morula stages, 48% of early blastocysts and 78% of late blastocysts. The number of Ang-1-expressing embryos in the early-blastocyst group was significantly different in comparison with zygotes, 4-cell-embryos, 8-cell-embryos and late blastocysts. Angiopoietin-2 mRNA and protein expression could not be detected in preimplantation embryos. Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase. Herein, Ang-1 expression in preimplantation mouse embryos as well as Ang-1 and -2 expression in mouse uteri is demonstrated, suggesting a possible role for angiopoietins in the embryo–maternal dialogue of the implantation process via an enhancement of the vascular remodelling in favour of an implanting conceptus.

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Hultström, Michael, Karin Fromell, Anders Larsson, Barbro Persson, Bo Nilsson, Susan E. Quaggin, Christer Betsholtz, Robert Frithiof, Miklos Lipcsey, and Marie Jeansson. "Angiopoietin-2 Inhibition of Thrombomodulin-Mediated Anticoagulation—A Novel Mechanism That May Contribute to Hypercoagulation in Critically Ill COVID-19 Patients." Biomedicines 10, no. 6 (June 6, 2022): 1333. http://dx.doi.org/10.3390/biomedicines10061333.

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Hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections, but the molecular mechanisms involved are unclear. Increased plasma levels of the inflammatory cytokine and TIE2 receptor antagonist Angiopoietin-2 were reported in severely ill COVID-19 patients. In vitro experiments suggest that Angiopoietin-2 bind and inhibits thrombomodulin. Thrombomodulin is expressed on the luminal surface of endothelial cells where it is an important member of the intrinsic anticoagulant pathway through activation of protein C. Using clinical data, mouse models, and in vitro assays, we tested if Angiopoietin-2 plays a causal role in COVID-19-associated hypercoagulation through direct inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Angiopoietin-2 was measured in 61 patients at admission, and after 10 days in the 40 patients remaining in the ICU. We found that Angiopoietin-2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. In support of a direct effect of Angiopoietin-2 on coagulation, we found that injected Angiopoietin-2 in mice associated to thrombomodulin and resulted in a shortened tail bleeding time, decreased circulating levels of activated protein C, and increased plasma thrombin/antithrombin complexes. Conversely, bleeding time was increased in endothelial-specific Angiopoietin-2 knockout mice, while knockout of Tie2 had no effect on tail bleeding. Using in vitro assays, we found that Angiopoietin-2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data suggest a novel in vivo mechanism for Angiopoietin-2 in COVID-19-associated hypercoagulation, implicating that Angiopoietin-2 inhibitors may be effective in the treatment of hypercoagulation in severe COVID-19 infection.

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Moxon, Joseph V., Alexandra F. Trollope, Brittany Dewdney, Catherine de Hollander, Domenico R. Nastasi, Jane M. Maguire, and Jonathan Golledge. "The effect of angiopoietin-1 upregulation on the outcome of acute ischaemic stroke in rodent models: A meta-analysis." Journal of Cerebral Blood Flow & Metabolism 39, no. 12 (October 4, 2019): 2343–54. http://dx.doi.org/10.1177/0271678x19876876.

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Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood–brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: –3.02; 95% confidence intervals: –4.41, –1.63; p < 0.001; n = 171 animals) and improved blood–brain barrier integrity (standardized mean difference: –2.02; 95% confidence intervals: –3.27, –0.77; p = 0.002; n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood–brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.

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Guan, Zhengbing, Guolin Cai, Junyong Sun, and Jian Lu. "Identification and expression analysis of bovine ANGPTL gene family." Current Zoology 56, no. 4 (August 1, 2010): 445–53. http://dx.doi.org/10.1093/czoolo/56.4.445.

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Abstract Encoded by seven genes, angiopoietin-like (ANGPTL) family members structurally similar to the angiogenic regulating factor angiopoietin are known to possess biological activities in angiogenesis and metabolism. Here we reports for the first time the identification and expression analysis of all the seven members of bovine ANGPTL gene family, which were designated bANGPTL1 to bANGPTL7 in order. The seven bANGPTL genes consist of 4-9 exons, span 3800-43000 bp and are located on different chromosomes. The deduced amino acid sequences of the members all possess an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain, both characteristics of angiopoietins. Phylogenetic analysis showed that the 32 identified ANGPTL homologs from 9 species could be classified into two major groups. Real-time quantitative PCR (Q-PCR) analysis revealed that the bANGPTL family members have different expression patterns. This study will be helpful for investigation on the biological role of the bANGPTL family in this economically important species. Furthermore, it provides an insight into the molecular evolution of the emerging ANGPTL family.

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CHEN, SHAOMIN, LIJUN GUO, BAOXIA CHEN, LIJIE SUN, and MING CUI. "Association of serum angiopoietin-1, angiopoietin-2 and angiopoietin-2 to angiopoietin-1 ratio with heart failure in patients with acute myocardial infarction." Experimental and Therapeutic Medicine 5, no. 3 (January 14, 2013): 937–41. http://dx.doi.org/10.3892/etm.2013.893.

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Villa, Erica, Rosina Critelli, Simone Lasagni, Alessandra Melegari, Angela Curatolo, Ciro Celsa, Dante Romagnoli, et al. "Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19." Blood Advances 5, no. 3 (February 1, 2021): 662–73. http://dx.doi.org/10.1182/bloodadvances.2020003736.

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Abstract This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.

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Oike, Yuichi, and Mitsuhisa Tabata. "Angiopoietin-Like Proteins." Circulation Journal 73, no. 12 (2009): 2192–97. http://dx.doi.org/10.1253/circj.cj-09-0710.

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El Sawy, Dina H., Nagwa A. Mohamed, Azza El Hamshary, Huda Marzouk, Sally R. Eid, Hanan A. Fathy, Amr S. Megawer, Azza K. Amer, Khadiga A. Salem, and Manal M. Badawy. "Serum angiopoietin-2." Medical Research Journal 14, no. 1 (June 2015): 12–17. http://dx.doi.org/10.1097/01.mjx.0000464334.22480.6d.

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Wang, Xiao, and Kiran Musunuru. "Angiopoietin-Like 3." JACC: Basic to Translational Science 4, no. 6 (October 2019): 755–62. http://dx.doi.org/10.1016/j.jacbts.2019.05.008.

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Saeed Masood, Hussien, Sami Akreem Zbaar, and Bushra Mustafa Mohamed. "Evaluation of Angiopoietin One and Angiopoietin Two with Missed Abortion." Indian Journal of Public Health Research & Development 11, no. 2 (February 1, 2020): 1241. http://dx.doi.org/10.37506/v11/i2/2020/ijphrd/194990.

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Saeed Masood, Hussien, Sami Akreem Zbaar, and Bushra Mustafa Mohamed. "Evaluation of Angiopoietin One and Angiopoietin Two with Missed Abortion." Indian Journal of Public Health Research & Development 11, no. 1 (January 1, 2020): 1165. http://dx.doi.org/10.37506/v11/i1/2020/ijphrd/193997.

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Machein, Marcia, Annette Knedla, Wagner Shawn, Elvira Neuschl, and Karl Plate. "ROLE OF ANGIOPOIETIN-1 AND ANGIOPOIETIN-2 IN GLIOMA ANGIOGENESIS." Cardiovascular Pathology 13, no. 3 (May 2004): 166. http://dx.doi.org/10.1016/j.carpath.2004.03.499.

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Torimura, Takuji, Takato Ueno, Motoaki Kin, Riko Harada, Eitaro Taniguchi, Toru Nakamura, Ryuichiro Sakata, et al. "Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma." Journal of Hepatology 40, no. 5 (May 2004): 799–807. http://dx.doi.org/10.1016/j.jhep.2004.01.027.

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Sokolovska, Jelizaveta, Juris Stefanovics, Gita Gersone, Leonora Pahirko, Janis Valeinis, Sanita Kalva-Vaivode, Vita Rovite, Leons Blumfelds, Valdis Pirags, and Peteris Tretjakovs. "Angiopoietin 2 and Neuropeptide Y are Associated with Diabetic Kidney Disease in Type 1 Diabetes Mellitus." Experimental and Clinical Endocrinology & Diabetes 128, no. 10 (January 20, 2020): 654–62. http://dx.doi.org/10.1055/a-1079-4711.

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Abstract Background Serum angiopoietin 2 levels have been associated with endothelial dysfunction and diabetic kidney disease. Derangements in autonomous nervous system lead to increased production of vasoconstrictory and angiogenic mediators such as norepinephrine and neuropeptide Y and are associated with increased risk of microvascular complications. Aim To investigate associations between angiopoietin 2, neuropeptide Y and diabetic kidney disease in patients with type 1 diabetes mellitus. Methods 289 patients with type 1 diabetes mellitus duration > 1 year were included. Patients were stratified according to presence of diabetic nephropathy (macroalbuminuria, estimated glomerular filtration rate<60 ml/min/1.73 m2 or end-stage renal disease). Angiopoietin 2 was measured by Luminex technology. Neuropeptide Y was measured by ELISA. Results Patients with diabetic nephropathy had significantly increased levels of angiopoietin 2 (4020.5 (2172.4–5778.1) pg/ml vs. 2001.0 (1326.7–2862.7) pg/ml) and neuropeptide Y (18.22 (14.85–21.85) ng/ml vs. 12.91 (9.96–17.07) ng/ml). Higher levels of angiopoietin 2 and neuropeptide Y were observed also in patients with arterial hypertension. Angiopoietin 2 and neuropeptide Y correlated significantly (ρ=0.245, p<0.001). Both biomarkers were significant predictors of estimated glomerular filtration rate and diabetic nephropathy in univariate regression models. In the fully adjusted regression models and after application of a stepwise selection regression method, angiopoietin 2 demonstrated a stronger predictive power for diabetic nephropathy compared to neuropeptide Y. Conclusion Diabetic nephropathy is associated with increased serum concentrations of angiopoietin 2 (marker of endothelial dysfunction) and neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin 2 is a more potent predictor of diabetic nephropathy compared to neuropeptide Y.

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Akmal, Mayetti, Amirah Zatil Izzah, Jamsari, Eriyati Darwin, and Dadang Hudaya Somasetia. "The Role of Angiopoietin-2 Gene Mutation on Clinical Severity of Dengue Disease in Children." Open Access Macedonian Journal of Medical Sciences 8, B (October 19, 2020): 1110–15. http://dx.doi.org/10.3889/oamjms.2020.5288.

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BACKGROUND: In general, angiopoietin-2 levels are increased concomitantly with dengue clinical severity. AIM: This research aims to determine the role of mutation on angiopoietin-2 on dengue clinical severity. METHODS: A cross-sectional study of 108 children with dengue disease grouped by severity. Angiopoietin-2 level was examined by enzyme-linked immunosorbent assay. Polymerase chain reaction and double nucleic acid sequencing are using 2 Exon 4-F primers. RESULTS: Angiopoietin-2 levels on rs7834131 mutant are higher in dengue fever (p < 0.05) and dengue hemorrhage fever group than non-mutant, while on dengue shock syndrome, it is lower than non-mutant. CONCLUSION: Angiopoietin-2 mutation on rs7834131 might have a protective effect on dengue disease severity.

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Phelps, Eric D., Dawn L. Updike, Elizabeth C. Bullen, Paula Grammas, and Eric W. Howard. "Transcriptional and posttranscriptional regulation of angiopoietin-2 expression mediated by IGF and PDGF in vascular smooth muscle cells." American Journal of Physiology-Cell Physiology 290, no. 2 (February 2006): C352—C361. http://dx.doi.org/10.1152/ajpcell.00050.2005.

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Angiopoietins play a significant role in vascular development and angiogenesis. Both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) bind the receptor tyrosine kinase Tie2. However, while Ang1 signaling results in the stabilization of vessel structure, Ang2 has been linked to vascular instability. The ratio of these two Tie2 ligands is thus critical for vascular stability and remodeling. This study identifies a mechanism of growth factor-mediated reduction in Ang2 expression in vascular smooth muscle cells (VSMCs). In response to PDGF, VSMCs downregulated Ang2 mRNA levels by 75% within 4 h, with a subsequent decrease in Ang2 protein levels. Quantitation of endogenous transcription rates revealed that PDGF stimulation did not alter Ang2 transcription rates, but instead induced a posttranscriptional mechanism of rapid Ang2 mRNA destabilization. The Ang2 mRNA half-life was reduced by at least 50% after PDGF treatment. The PDGF-induced mRNA turnover mechanism was dependent on several MAPK pathways, including ERK and JNK. In contrast, IGF-I, which did not significantly activate ERK or JNK, stimulated increased Ang2 expression through transcriptional activation. These findings demonstrate that VSMCs adjust Ang2 expression through multiple mechanisms, including changes in transcription as well as posttranscriptional mRNA destabilization.

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Matsuoka-Sakata, Aki, Hiroshi Tamura, Hiromi Asada, Ichiro Miwa, Toshiaki Taketani, Yoshiaki Yamagata, and Norihiro Sugino. "Changes in vascular leakage and expression of angiopoietins in the corpus luteum during pregnancy in rats." Reproduction 131, no. 2 (February 2006): 351–60. http://dx.doi.org/10.1530/rep.1.00947.

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The present study investigates changes in blood vessel stability and its regulation in the corpus luteum (CL) during pregnancy in the rat. First, blood vessel stability in the CL was evaluated during pregnancy based on vascular leakage, which was quantified by the Evans blue assay. Vascular leakage was highest on day 3, thereafter decreased until day 15 and increased again on day 21. Secondly, to study the regulation of vascular leakage, the expression of angiopoietins was examined in the CL during pregnancy. Angiopoietin-1 (Ang-1) effects maturation and stabilization of newly formed blood vessels, while Ang-2 produces the opposite effect by allowing vascular remodeling. An immunohistochemical study showed both Ang-1 and Ang-2 expression in luteal cells. mRNA and protein levels of Ang-1 were significantly higher on days 12 and 15 than those on days 3 and 21, whereas there was no significant change in Ang-2 expression. Since estradiol contributes to CL development during mid-pregnancy, we finally studied whether estradiol regulates vascular leakage and angiopoietin expression. Rats undergoing hypophysectomy and hysterectomy (hypox-hect) on day 12 were treated with estradiol until day 15. Vascular leakage was increased and Ang-1 expression was decreased by hypox-hect, and these effects were completely reversed by estradiol treatment. In conclusion, blood vessel stability in the CL is likely to be associated with CL development and CL regression, and may be regulated by angiopoietins. Estradiol contributes to blood vessel stabilization in the CL during mid-pregnancy, which is associated with an increase in Ang-1 expression.

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Chen, Shaomin, Lijun Guo, Ming Cui, Lijie Sun, and Lin Mi. "Dynamic changes in serum angiopoietin-1, angiopoietin-2, and angiopoietin-2/angiopoietin-1 ratio in acute myocardial infarction patients treated with primary percutaneous coronary intervention." Biomarkers 17, no. 5 (May 30, 2012): 441–46. http://dx.doi.org/10.3109/1354750x.2012.684152.

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Kapiainen, Emmi, Harri Elamaa, Ilkka Miinalainen, Valerio Izzi, and Lauri Eklund. "Cooperation of Angiopoietin-2 and Angiopoietin-4 in Schlemm's Canal Maintenance." Investigative Opthalmology & Visual Science 63, no. 11 (October 3, 2022): 1. http://dx.doi.org/10.1167/iovs.63.11.1.

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Lee, Yang Deok, Hyeon Kyu Go, Yoon Jin Kwak, and Yong Soo Cho. "ROLES OF ANGIOPOIETIN-1 AND ANGIOPOIETIN-2 IN SMOKE INHALATION INJURY." Chest 134, no. 4 (October 2008): 90P. http://dx.doi.org/10.1378/chest.134.4_meetingabstracts.p90002.

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Ahmad, Syed A., Wenbiao Liu, Young D. Jung, Fan Fan, Niels Reinmuth, Corazon D. Bucana, and Lee M. Ellis. "Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma." Cancer 92, no. 5 (2001): 1138–43. http://dx.doi.org/10.1002/1097-0142(20010901)92:5<1138::aid-cncr1431>3.0.co;2-l.

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K., Kishan Raj. "Angiopoietin 2 in type 2 diabetes mellitus patients and those with complications: an observational comparative study." International Journal of Advances in Medicine 7, no. 5 (April 23, 2020): 733. http://dx.doi.org/10.18203/2349-3933.ijam20201606.

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Background: Angiopoietin 2 levels in blood signifies neo vascularization. Only biomarker available now for routine check up is HbA1c. However, it doesn’t suggest if patient is more prone to get into complications than the other. Here, we try to bring in another biomarker Angiopoietin 2 and elucidate if it can identify patients going in for complications of type 2 diabetes mellitus early.Methods: Total 60 diabetic patients were studied over a span of 1 year. 30 were diabetic without any complciations and another 30 were with complications (Diabetic foot ulcer, Diabetic retinopathy, Diabetic nephropathy, Diabetic neuropathy). Angiopoietin 2 levels were estimated in both the groups and compared.Results: Analysis showed Mean duration of Diabetes was significantly lower in patients without complication than those with complications. Human angiopoietin 2 levels were elevated in both the study groups. More so, in the study group with Diabetic patients with complications. It was statistically significant. (p<0.001).There was no significant relationship between duration of diabetes and Human angiopoietin 2 levels.Conclusions: It was found that angiopoietin 2 is also a good biomarker for diabetes as HbA1c. It also helps in detection of complications earlier and thus may help in reducing morbidity as well as mortality. Further studies are required to strengthen the information got from this study to compare efficacy of HbA1c and angiopoietin 2 as well as how early can we detect the patients who may land up in complications.

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Singh, Harprit, Tariq A. Tahir, Deborah O. A. Alawo, Eyad Issa, and Nicholas P. J. Brindle. "Molecular control of angiopoietin signalling." Biochemical Society Transactions 39, no. 6 (November 21, 2011): 1592–96. http://dx.doi.org/10.1042/bst20110699.

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The angiopoietins act through the endothelial receptor tyrosine kinase Tie2 to regulate vessel maturation in angiogenesis and control quiescence and stability of established vessels. The activating ligand, Ang1 (angiopoietin-1), is constitutively expressed by perivascular cells, and the ability of endothelial cells to respond to the ligand is controlled at the level of the Ang1 receptor. This receptor interacts with the related protein Tie1 on the cell surface, and Tie1 inhibits Ang1 signalling through Tie2. The responsiveness of endothelium to Ang1 is determined by the relative levels of Tie2 and the inhibitory co-receptor Tie1 in the cells. Tie1 undergoes regulated ectodomain cleavage which is stimulated by a range of factors including VEGF (vascular endothelial growth factor), inflammatory cytokines and changes in shear stress. Ectodomain cleavage of Tie1 relieves inhibition of Tie2 and enhances Ang1 signalling. This mechanism regulates Ang1 signalling without requiring changes in the level of the ligand and allows Ang1 signalling to be co-ordinated with other signals in the cellular environment. Regulation of signalling at the level of receptor responsiveness may be an important adaptation in systems in which an activating ligand is normally present in excess or where the ligand provides a constitutive maintenance signal.

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Mansour, Sherry G., Pavan K. Bhatraju, Steven G. Coca, Wassim Obeid, Francis P. Wilson, Ian B. Stanaway, Yaqi Jia, et al. "Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury." Journal of the American Society of Nephrology 33, no. 3 (January 11, 2022): 613–27. http://dx.doi.org/10.1681/asn.2021060757.

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BackgroundThe mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure.MethodsTo investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later.ResultsMedian age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression.ConclusionsA higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

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Journal articles on the topic 'Angiopoietin'

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