Journal articles: 'Neovascularization Regulation'

1

Murakami, Masahiro, and Michael Simons. "Fibroblast growth factor regulation of neovascularization." Current Opinion in Hematology 15, no. 3 (May 2008): 215–20. http://dx.doi.org/10.1097/moh.0b013e3282f97d98.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Wary, Kishore K., Erin E. Kohler, and Ishita Chatterjee. "Focal adhesion kinase regulation of neovascularization." Microvascular Research 83, no. 1 (January 2012): 64–70. http://dx.doi.org/10.1016/j.mvr.2011.05.002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Terao, Ryo, and Hiroki Kaneko. "Lipid Signaling in Ocular Neovascularization." International Journal of Molecular Sciences 21, no. 13 (July 4, 2020): 4758. http://dx.doi.org/10.3390/ijms21134758.

Full text

Abstract:

Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.

APA, Harvard, Vancouver, ISO, and other styles

4

Leonhardt, Franziska, Sebastian Grundmann, Martin Behe, Franziska Bluhm, Rebecca A. Dumont, Friederike Braun, Melpomeni Fani, et al. "Inflammatory neovascularization during graft-versus-host disease is regulated by αv integrin and miR-100." Blood 121, no. 17 (April 25, 2013): 3307–18. http://dx.doi.org/10.1182/blood-2012-07-442665.

Full text

Abstract:

Key Points Our data from the mouse model and patients indicate that inflammatory neovascularization during GvHD is targetable via αv integrin. We identify a negative regulation of GvHD-related neovascularization by miR-100.

APA, Harvard, Vancouver, ISO, and other styles

5

Xiang, Guosheng, Michael D. Schuster, Tetsunori Seki, Alfred A. Kocher, Shawdee Eshghi, Andrew Boyle, and Silviu Itescu. "Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors." Journal of Experimental Medicine 200, no. 12 (December 13, 2004): 1657–66. http://dx.doi.org/10.1084/jem.20040221.

Full text

Abstract:

Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult.

APA, Harvard, Vancouver, ISO, and other styles

6

Ishida, Susumu, Tomohiko Usui, Kenji Yamashiro, Yuichi Kaji, Shiro Amano, Yuichiro Ogura, Tetsuo Hida, et al. "VEGF164-mediated Inflammation Is Required for Pathological, but Not Physiological, Ischemia-induced Retinal Neovascularization." Journal of Experimental Medicine 198, no. 3 (August 4, 2003): 483–89. http://dx.doi.org/10.1084/jem.20022027.

Full text

Abstract:

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte–mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.

APA, Harvard, Vancouver, ISO, and other styles

7

Burtenshaw, Denise, and Paul A. Cahill. "Natriuretic Peptides and the Regulation of Retinal Neovascularization." Arteriosclerosis, Thrombosis, and Vascular Biology 40, no. 1 (January 2020): 7–10. http://dx.doi.org/10.1161/atvbaha.119.313566.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Battinelli, Elisabeth M. "Platelet and Megakaryocytic Regulation of Tumor Progression." Blood 130, Suppl_1 (December 7, 2017): SCI—26—SCI—26. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-26.sci-26.

Full text

Abstract:

Traditionally viewed as the bandaids of the blood, the contribution of platelets to the progression of malignancy is emerging as a compelling focus for therapeutic intervention. Complex interactions between tumor cells, and circulating platelets play an important role in tumor growth and dissemination, and a growing body of data supports a role for platelet activation and release of chemokines in metastases and neovascularization. Supporting this concept is the evidence that elevated platelet counts (thrombocytosis) at time of diagnosis with malignancy is a harbinger of an aggressive cancer with a poor prognosis. One very interesting and provocative connection between cancer and platelets is the increasing evidence that tumor cells hijack platelets to promote a more pro-malignant phenotype to drive disease progression. Our laboratories have been instrumental in establishing the pro-malignant role of platelets in metastasis and neovascularization. We have demonstrated that tumor cells can instruct platelets to release key cytokines that promote angiogenesis and metastasis of tumor cells. Perhaps the most compelling clinical evidence of the link between platelets and malignancy is the finding that anti-platelet agents can have a profound impact on malignancy. We have demonstrated previously, anti-platelet agents such as aspirin and anticoagulants suppress release of key neovascularization factors from platelets and suppress the neovascularization potential. Aspirin also suppresses the invasive properties of platelets in mouse metastasis models as well as in vitro metastasis assays. Similarly, we have also demonstrated that tamoxifen, a selective estrogen receptor modulator often used to treat breast cancer, can also diminish the ability of platelets to support malignancy by diminishing the platelet's role in promoting neovascularization as well as metastasis. Although much is understood regarding how tumors communicate with platelets less is understood about how platelets manipulate tumor cells. Our laboratory has elucidated the role of key chemokines released from platelets in response to tumor cells and how these factors promote tumor growth and metastasis. We have recently discovered that tumor cells can instruct platelets to release CCL5, a known driver of tumor cell invasion and metastasis, and have expanded the role of CCL5 not only as a regulator of metastasis but also as a central controller of platelet production. Despite this progress many questions still remain regarding the interaction between tumor cells and platelets. We are particularly interested in how tumor cells instruct megakaryocytes to increase platelet production. In addition malignancy may also reprogram megakaryocytes thereby manipulating the platelet phenotype to support tumor growth and metastasis. Because most cancer therapies focus on the tumor itself, the idea of targeting platelets in the tumor microenvironment to arrest tumor growth and metastatic spread represents a novel therapeutic strategy. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

9

Walter, Dirk H., and Stefanie Dimmeler. "Endothelial Progenitor Cells: Regulation and Contribution to Adult Neovascularization." Herz 27, no. 7 (November 1, 2002): 579–88. http://dx.doi.org/10.1007/s00059-002-2427-y.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Li, Fengkai, Jiahui Xu, and Suling Liu. "Cancer Stem Cells and Neovascularization." Cells 10, no. 5 (April 30, 2021): 1070. http://dx.doi.org/10.3390/cells10051070.

Full text

Abstract:

Cancer stem cells (CSCs) refer to a subpopulation of cancer cells responsible for tumorigenesis, metastasis, and drug resistance. Increasing evidence suggests that CSC-associated tumor neovascularization partially contributes to the failure of cancer treatment. In this review, we discuss the roles of CSCs on tumor-associated angiogenesis via trans-differentiation or forming the capillary-like vasculogenic mimicry, as well as the roles of CSCs on facilitating endothelial cell-involved angiogenesis to support tumor progression and metastasis. Furthermore, we discuss the underlying regulation mechanisms, including the intrinsic signals of CSCs and the extrinsic signals such as cytokines from the tumor microenvironment. Further research is required to identify and verify some novel targets to develop efficient therapeutic approaches for more efficient cancer treatment through interfering CSC-mediated neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

11

Oladipupo, Sunday S., Song Hu, Andrea C. Santeford, Junjie Yao, Joanna R. Kovalski, Ralph V. Shohet, Konstantin Maslov, Lihong V. Wang, and Jeffrey M. Arbeit. "Conditional HIF-1 induction produces multistage neovascularization with stage-specific sensitivity to VEGFR inhibitors and myeloid cell independence." Blood 117, no. 15 (April 14, 2011): 4142–53. http://dx.doi.org/10.1182/blood-2010-09-307538.

Full text

Abstract:

Abstract Neovascularization is a crucial component of tumor growth and ischemia. Although prior work primarily used disease models, delineation of neovascularization in the absence of disease can reveal intrinsic mechanisms of microvessel regulation amenable to manipulation in illness. We created a conditional model of epithelial HIF-1 induction in adult mice (TetON-HIF-1 mice). Longitudinal photoacoustic microscopy (L-PAM) was coincidentally developed for noninvasive, label-free serial imaging of red blood cell-perfused vasculature in the same mouse for weeks to months. TetON-HIF-1 mice evidenced 3 stages of neovascularization: development, maintenance, and transgene-dependent regression. Regression occurred despite extensive and tight pericyte coverage. L-PAM mapped microvascular architecture and quantified volumetric changes in neocapillary morphogenesis, arteriovenous remodeling, and microvessel regression. Developmental stage endothelial proliferation down-regulation was associated with a DNA damage checkpoint consisting of p53, p21, and endothelial γ-H2AX induction. The neovasculature was temporally responsive to VEGFR2 immuno-blockade, with the developmental stage sensitive, and the maintenance stage resistant, to DC101 treatment. L-PAM analysis also pinpointed microvessels ablated or resistant to VEGFR2 immuno-blockade. HIF-1–recruited myeloid cells did not mediate VEGFR2 inhibitor resistance. Thus, HIF-1 neovascularization in the absence of disease is self-regulated via cell autonomous endothelial checkpoints, and resistant to angiogenesis inhibitors independent of myeloid cells.

APA, Harvard, Vancouver, ISO, and other styles

12

Zhang, Qiuhua, Dong Wang, Venkatesh Kundumani-Sridharan, Laxmisilpa Gadiparthi, Dianna A. Johnson, Gabor J. Tigyi, and Gadiparthi N. Rao. "PLD1-dependent PKCγ activation downstream to Src is essential for the development of pathologic retinal neovascularization." Blood 116, no. 8 (August 26, 2010): 1377–85. http://dx.doi.org/10.1182/blood-2010-02-271478.

Full text

Abstract:

Abstract Vascular endothelial growth factor (VEGF) appears to be an important mediator of pathologic retinal angiogenesis. In understanding the mechanisms of pathologic retinal neovascularization, we found that VEGF activates PLD1 in human retinal microvascular endothelial cells, and this event is dependent on Src. In addition, VEGF activates protein kinase C-γ (PKCγ) via Src-dependent PLD1 stimulation. Inhibition of Src, PLD1, or PKCγ via pharmacologic, dominant negative mutant, or siRNA approaches significantly attenuated VEGF-induced human retinal microvascular endothelial cell migration, proliferation, and tube formation. Hypoxia also induced Src-PLD1-PKCγ signaling in retina, leading to retinal neovascularization. Furthermore, siRNA-mediated down-regulation of VEGF inhibited hypoxia-induced Src-PLD1-PKCγ activation and neovascularization. Blockade of Src-PLD1-PKCγ signaling via the siRNA approach also suppressed hypoxia-induced retinal neovascularization. Thus, these observations demonstrate, for the first time, that Src-dependent PLD1-PKCγ activation plays an important role in pathologic retinal angiogenesis.

APA, Harvard, Vancouver, ISO, and other styles

13

Moses, M. A. "The Regulation of Neovascularization by Matrix Metalloproteinases and Their Inhibitors." Retina 18, no. 5 (May 1998): 494. http://dx.doi.org/10.1097/00006982-199805000-00039.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Zong, Rongrong, Tong Zhou, Zhirong Lin, Xiaorui Bao, Yanghui Xiu, Yanfeng Chen, Longlong Chen, Jian-xing Ma, Zuguo Liu, and Yueping Zhou. "Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization." Investigative Opthalmology & Visual Science 57, no. 3 (March 28, 2016): 1398. http://dx.doi.org/10.1167/iovs.15-17417.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Zhang, Jiahao, Shurong Wang, Yuxi He, Boyuan Yao, and Yan Zhang. "Regulation of matrix metalloproteinases 2 and 9 in corneal neovascularization." Chemical Biology & Drug Design 95, no. 5 (February 16, 2020): 485–92. http://dx.doi.org/10.1111/cbdd.13529.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Gao, Yushuo, Yisheng Zhong, Yanji Zhu, Anna M. Demetriades, Yujuan Cai, Jikui Shen, Qing Lu, Xi Shen, and Bing Xie. "Flt3 Regulation in the Mononuclear Phagocyte System Promotes Ocular Neovascularization." Journal of Ophthalmology 2018 (2018): 1–14. http://dx.doi.org/10.1155/2018/2518568.

Full text

Abstract:

Fms-like tyrosine kinase 3 (Flt3), a tyrosine kinase receptor expressed in CD34+ hematopoietic stem/progenitor cells, is important for both normal myeloid and lymphoid differentiation. It has been implicated in mice and humans for potential multilineage differentiation. We found that mice deficient in Flt3 or mice that received an Flt3 inhibitor (AC220) showed significantly reduced areas of ischemia-induced retinal neovascularization (RNV) and laser-induced choroidal NV (CNV) (P<0.05). Increased Flt3 expression at the protein level was detected in retinas of oxygen-induced retinopathy (OIR) mice at P15 and P18 during retinal NV (RNV) progression. We subsequently found that macrophages (Mphi) polarization was regulated at the site of CNV in Flt3-deficient mice. Flow cytometry analysis demonstrated that Flt3 deficiency shifted Mphi polarization towards an M2 phenotype during RNV with significant reduction in M1 cytokine expression when compared to the wild-type controls (P<0.05). Based on the above findings, we concluded that Flt3 inhibition alleviated ocular NV by promoting a Mphi polarization shift towards the M2 phenotype. Therapies targeting Flt3 may provide a new approach for the treatment of ocular NV.

APA, Harvard, Vancouver, ISO, and other styles

17

Moses, Marsha A. "The Regulation of Neovascularization by Matrix Metalloproteinases and Their Inhibitors." Stem Cells 15, no. 3 (May 1997): 180–89. http://dx.doi.org/10.1002/stem.150180.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Chan, Elsa C., Peter van Wijngaarden, Elsie Chan, Darleen Ngo, Jiang-Hui Wang, Hitesh M. Peshavariya, Gregory J. Dusting, and Guei-Sheung Liu. "NADPH oxidase 2 plays a role in experimental corneal neovascularization." Clinical Science 130, no. 9 (March 18, 2016): 683–96. http://dx.doi.org/10.1042/cs20150103.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Lutty, G. A., R. J. Mello, C. Chandler, C. Fait, A. Bennett, and A. Patz. "Regulation of cell growth by vitreous humour." Journal of Cell Science 76, no. 1 (June 1, 1985): 53–65. http://dx.doi.org/10.1242/jcs.76.1.53.

Full text

Abstract:

Extracts of normal vitreous have been found to inhibit angiogenesis in two animal models: tumour-induced neovascularization in the rabbit corneal micropocket and retinal extract-induced angiogenesis in the chick chorioallantoic membrane assay. Using in vitro assays, we have found recently that an extract of bovine vitreous, free of hyaluronic acid, inhibits proliferation of cells in the aortic wall, i.e. endothelium and smooth muscle cells, as well as capillary and corneal endothelium. The inhibition is dose-dependent, as determined by either cell count or [3H]thymidine incorporation, and not due to cytotoxicity, as demonstrated with a double-label thymidine assay. The inhibitor is trypsin-sensitive and heat-stable (95 degrees C for 10 min). Conversely, proliferation of pericytes, lens epithelium and fibroblasts (dermal and corneal) was stimulated by the vitreous extract. This mitogenic activity was heat-labile. Growth of pigment epithelium and several tumour cell lines was unaffected. The data demonstrate that normal vitreous contains a heat-stable growth inhibitor specific for endothelium and smooth muscle cells, and a non-specific heat-labile mitogen. The paradoxical effect of this antiangiogenic factor on arterial and capillary contractile cells, smooth muscle and pericytes, suggests a basic difference in the regulation of the two vasculatures. The results suggest that a substance in normal vitreous may be important in controlling neovascularization that results from diabetic and other retinopathies, and could be useful for inhibiting tumour-induced angiogenesis.

APA, Harvard, Vancouver, ISO, and other styles

20

Jamali, Nasim, Christine M. Sorenson, and Nader Sheibani. "Vitamin D and regulation of vascular cell function." American Journal of Physiology-Heart and Circulatory Physiology 314, no. 4 (April 1, 2018): H753—H765. http://dx.doi.org/10.1152/ajpheart.00319.2017.

Full text

Abstract:

Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for the treatment of various types of cancer and chronic diseases. We have previously shown that the active form of vitamin D [1,25(OH)2D3] is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis. Here, we review the important nutritional value of vitamin D and the abnormalities linked to its deficiency. We will explore its potential role as a regulator of angiogenesis and vascular cell function and the role vitamin D receptor (VDR) expression plays in these activities during vascular development and neovascularization. Our studies have established an important role for 1,25(OH)2D3 and VDR in the regulation of perivascular supporting cell function. In addition, the interaction of 1,25(OH)2D3 and VDR is essential for these activities and inhibition of neovascularization. Delineating the signaling pathways involved and identification of genes that are the target of 1,25(OH)2D3 regulation in vascular cells will allow us to identify novel pathways that are targets for regulation of vascular function and angiogenesis.

APA, Harvard, Vancouver, ISO, and other styles

21

Sun, Ye, Chi-Hsiu Liu, John Paul SanGiovanni, Lucy P. Evans, Katherine T. Tian, Bing Zhang, Andreas Stahl, et al. "Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation." Proceedings of the National Academy of Sciences 112, no. 33 (August 4, 2015): 10401–6. http://dx.doi.org/10.1073/pnas.1504387112.

Full text

Abstract:

Pathologic ocular angiogenesis is a leading cause of blindness, influenced by both dysregulated lipid metabolism and inflammation. Retinoic-acid-receptor–related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor with diverse biologic function including regulation of lipid metabolism and inflammation; however, its role in pathologic retinal angiogenesis remains poorly understood. Using a mouse model of oxygen-induced proliferative retinopathy, we showed that RORα expression was significantly increased and genetic deficiency of RORα substantially suppressed pathologic retinal neovascularization. Loss of RORα led to decreased levels of proinflammatory cytokines and increased levels of antiinflammatory cytokines in retinopathy. RORα directly suppressed the gene transcription of suppressors of cytokine signaling 3 (SOCS3), a critical negative regulator of inflammation. Inhibition of SOCS3 abolished the antiinflammatory and vasoprotective effects of RORα deficiency in vitro and in vivo. Moreover, treatment with a RORα inverse agonist SR1001 effectively protected against pathologic neovascularization in both oxygen-induced retinopathy and another angiogenic model of very-low–density lipoprotein receptor (Vldlr)-deficient (Vldlr−/−) mice with spontaneous subretinal neovascularization, whereas a RORα agonist worsened oxygen-induced retinopathy. Our data demonstrate that RORα is a novel regulator of pathologic retinal neovascularization, and RORα inhibition may represent a new way to treat ocular neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

22

Ravi, Rajani, Bijoyesh Mookerjee, Zaver M. Bhujwalla, Carrie Hayes Sutter, Dmitri Artemov, Qinwen Zeng, Larry E. Dillehay, Ashima Madan, Gregg L. Semenza, and Atul Bedi. "Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α." Genes & Development 14, no. 1 (January 1, 2000): 34–44. http://dx.doi.org/10.1101/gad.14.1.34.

Full text

Abstract:

The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1α subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1α levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor (VEGF) gene in response to hypoxia. Forced expression of HIF-1α in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.

APA, Harvard, Vancouver, ISO, and other styles

23

Wei, Yanhong, Junsong Gong, Zhenhua Xu, Rajesh K. Thimmulappa, Katherine L. Mitchell, Derek S. Welsbie, Shyam Biswal, and Elia J. Duh. "Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A." Proceedings of the National Academy of Sciences 112, no. 50 (November 30, 2015): E6927—E6936. http://dx.doi.org/10.1073/pnas.1512683112.

Full text

Abstract:

Delayed revascularization of ischemic neural tissue is a major impediment to preservation of function in central nervous system (CNS) diseases including stroke and ischemic retinopathies. Therapeutic strategies allowing rapid revascularization are greatly needed to reduce ischemia-induced cellular damage and suppress harmful pathologic neovascularization. However, key mechanisms governing vascular recovery in ischemic CNS, including regulatory molecules governing the transition from tissue injury to tissue repair, are largely unknown. NF-E2-related factor 2 (Nrf2) is a major stress-response transcription factor well known for its cell-intrinsic cytoprotective function. However, its role in cell–cell crosstalk is less appreciated. Here we report that Nrf2 is highly activated in ischemic retina and promotes revascularization by modulating neurons in their paracrine regulation of endothelial cells. Global Nrf2 deficiency strongly suppresses retinal revascularization and increases pathologic neovascularization in a mouse model of ischemic retinopathy. Conditional knockout studies demonstrate a major role for neuronal Nrf2 in vascular regrowth into avascular retina. Deletion of neuronal Nrf2 results in semaphorin 6A (Sema6A) induction in hypoxic/ischemic retinal ganglion cells in a hypoxia-inducible factor-1 alpha (HIF-1α)-dependent fashion. Sema6A expression increases in avascular inner retina and colocalizes with Nrf2 in human fetal eyes. Extracellular Sema6A leads to dose-dependent suppression of the migratory phenotype of endothelial cells through activation of Notch signaling. Lentiviral-mediated delivery of Sema6A small hairpin RNA (shRNA) abrogates the defective retinal revascularization in Nrf2-deficient mice. Importantly, pharmacologic Nrf2 activation promotes reparative angiogenesis and suppresses pathologic neovascularization. Our findings reveal a unique function of Nrf2 in reprogramming ischemic tissue toward neurovascular repair via Sema6A regulation, providing a potential therapeutic strategy for ischemic retinal and CNS diseases.

APA, Harvard, Vancouver, ISO, and other styles

24

Lim, Dansaem, Jin Gu Cho, Eunsik Yun, Aram Lee, Hong-Yeoul Ryu, Young Joo Lee, Sukjoon Yoon, et al. "MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells." Genes 12, no. 1 (December 23, 2020): 9. http://dx.doi.org/10.3390/genes12010009.

Full text

Abstract:

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

25

Kase, Satoru, Shikun He, Shozo Sonoda, Mizuki Kitamura, Christine Spee, Eric Wawrousek, Stephen J. Ryan, Ram Kannan, and David R. Hinton. "αB-crystallin regulation of angiogenesis by modulation of VEGF." Blood 115, no. 16 (April 22, 2010): 3398–406. http://dx.doi.org/10.1182/blood-2009-01-197095.

Full text

Abstract:

Abstract αB-crystallin is a chaperone belonging to the small heat shock protein family. Herein we show attenuation of intraocular angiogenesis in αB-crystallin knockout (αB-crystallin−/−) mice in 2 models of intraocular disease: oxygen-induced retinopathy and laser-induced choroidal neovascularization. Vascular endothelial growth factor A (VEGF-A) mRNA and hypoxia inducible factor-1α protein expression were induced during retinal angiogenesis, but VEGF-A protein expression remained low in αB-crystallin−/− retina versus wild-type mice, whereas VEGF-R2 expression was not affected. Both αB-crystallin and its phosphorylated serine59 formwere expressed, and immunoprecipitation revealed αB-crystallin binding to VEGF-A but not transforming growth factor-β in cultured retinal pigment epithelial (RPE) cells. αB-crystallin and VEGF-A are colocalized in the endoplasmic reticulum in RPE cells under chemical hypoxia. αB-crystallin−/− RPE showed low VEGF-A secretion under serum-starved conditions compared with wild-type cells. VEGF-A is polyubiquitinated in control and αB-crystallin siRNA treated RPE; however, mono-tetra ubiquitinated VEGF-A increases with αB-crystallin knockdown. Endothelial cell apoptosis in newly formed vessels was greater in αB-crystallin−/− than wild-type mice. Proteasomal inhibition in αB-crystallin−/− mice partially restores VEGF-A secretion and angiogenic phenotype in choroidal neovascularization. Our studies indicate an important role for αB-crystallin as a chaperone for VEGF-A in angiogenesis and its potential as a therapeutic target.

APA, Harvard, Vancouver, ISO, and other styles

26

Mizukami, Yusuke, Junpei Sasajima, Kazumasa Nakamura, Kazuya Sato, Yoshiaki Sugiyama, Madoka Yamazaki, Toru Kawamoto, et al. "Hedgehog Promotes Neovascularization through the Regulation of Bone-Marrow Derived Progenitors." Blood 114, no. 22 (November 20, 2009): 3048. http://dx.doi.org/10.1182/blood.v114.22.3048.3048.

Full text

Abstract:

Abstract Abstract 3048 Poster Board II-1024 The hedgehog (Hh) pathway has been implicated in the development of embryonic blood vessels and pathogenesis of cancer. Smoothened (Smo), one of the receptors in Hh signaling, is a promising molecular target for the treatment of malignancies. Pancreatic ductal adenocarcinoma (PDAC) is one of the tumors in which sonic hedgehog (Shh) is misexpressed. Although there are cell-autonomous effects of Hh on the proliferation of tumor cells, recent studies have demonstrated an oncogenic function of Hh in stromal cells. Cyclopamine antagonizes Smo and can attenuate PDAC growth in mice, resulting in regression of the tumor vasculature with reduced pericyte coverage. However, the inhibitory effect of cyclopamine on proliferation of KP-1N cells, a human PDAC line highly expressing Shh, was modest, indicating additional effects of Hh signaling on tumor progression. Here, we have identified novel molecular mechanisms by which Hh regulates tumor angiogenesis. Expression of Gli2 protein in the stroma, but not in cancer cells, was attenuated markedly by cyclopamine administration, consistent with the general absence of autocrine Hh signaling in PDAC cells. Cyclopamine significantly attenuated the homing of bone marrow (BM)-derived cells into KP-1N xenografts and their interaction with the tumor vasculature, suggesting that Hh signaling may play a role during migration and differentiation of BM-derived progenitors to participate in neovascularization. Host derived Ang-1 and IGF-1 mRNA levels in xenografts were strongly downregulated by cyclopamine, which may contribute to the maintenance and maturation of tumor vasculature. In vitro co-culture experiments demonstrated that KP-1N cells induced Ang-1/IGF-1 production in BM-progenitors (c-Kit+ fraction of BM mononuclear cell), and this induction was significantly attenuated either by cyclopamine or lentiviral shRNA targeting Smo. In addition, in vitro tube formation assay with the mouse endothelial line MS-1 and a matrigel plug assay supports the role of Shh secreted from PDAC cells to induce migration and capillary formation of BM-derived progenitors. IGF-1 is a crucial target of Hh signaling in BM-derived cells during neovascularization, since anti-IGF-1 neutralizing antibody blocked the induction of the capillary morphogenesis by BM-progenitors. Finally, this “paracrine” effect of Hh seems to be a late event during pancreatic tumorigenesis, as stromal Patch1/Gli2 expression was detected within PDAC lesions in Pdx1-Cre;LSL-KrasG12D;p53lox/+ mice, but not in PanIN lesion, a potential precursor of PDAC, in Pdx1-Cre;LSL-KrasG12D mice. We also observed upregulation of VE-cadherin and Ptch1 mRNA in lineage–/c-Kit+ fraction of BM mononuclear cells (primitive BM-derived progenitors) from PDAC mice as compared to wild-type/PanIN mice, suggesting that pro-angiogenic conditions are prepared at the level of the BM in cancer-bearing hosts. The primitive progenitors derived from ‘activated BM’ are imported to the tumor microenvironment where they become fully activated. Hh-ligand from cancer cells can therefore have a profound effect on neovascularization through the regulation of the progenitors during late stages of tumorigenesis. This work was supported by New Energy and Industrial Technology Development Organization (NEDO) of Japan. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

27

Mehta, Dolly. "Focal adhesion kinase regulation of endothelial barrier function, apoptosis, and neovascularization." Microvascular Research 83, no. 1 (January 2012): 1–2. http://dx.doi.org/10.1016/j.mvr.2011.10.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Muether, Philipp S., Susanne Dell, Norbert Kociok, Grit Zahn, Roland Stragies, Doerte Vossmeyer, and Antonia M. Joussen. "The role of integrin α5β1 in the regulation of corneal neovascularization." Experimental Eye Research 85, no. 3 (September 2007): 356–65. http://dx.doi.org/10.1016/j.exer.2007.06.004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Mahdipour, Elahe, Jayne C. Charnock, and Kimberly A. Mace. "Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells." Blood 117, no. 3 (January 20, 2011): 815–26. http://dx.doi.org/10.1182/blood-2009-12-259549.

Full text

Abstract:

Abstract Injury induces the recruitment of bone marrow-derived cells (BMDCs) that contribute to the repair and regeneration process. The behavior of BMDCs in injured tissue has a profound effect on repair, but the regulation of BMDC behavior is poorly understood. Aberrant recruitment/retention of these cells in wounds of diabetic patients and animal models is associated with chronic inflammation and impaired healing. BMD Gr-1+CD11b+ cells function as immune suppressor cells and contribute significantly to tumor-induced neovascularization. Here we report that Gr-1+CD11b+ cells also contribute to injury-induced neovascularization, but show altered recruitment/retention kinetics in the diabetic environment. Moreover, diabetic-derived Gr-1+CD11b+ cells fail to stimulate neovascularization in vivo and have aberrant proliferative, chemotaxis, adhesion, and differentiation potential. Previously we demonstrated that gene transfer of HOXA3 to wounds of diabetic mice is taken up by and expressed by recruited BMDCs. This is associated with a suppressed inflammatory response, enhanced neovascularization, and accelerated wound healing. Here we show that sustained expression of Hoxa3 in diabetic-derived BMD Gr-1+CD11b+ cells reverses their diabetic phenotype. These findings demonstrate that manipulation of adult stem/progenitor cells ex vivo could be used as a potential therapy in patients with impaired wound healing.

APA, Harvard, Vancouver, ISO, and other styles

30

Onimaru, Mitsuho, Yoshikazu Yonemitsu, Takaaki Fujii, Mitsugu Tanii, Toshiaki Nakano, Kazunori Nakagawa, Ri-ichiro Kohno, Mamoru Hasegawa, Shin-ichi Nishikawa, and Katsuo Sueishi. "VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 5 (November 2009): H1685—H1696. http://dx.doi.org/10.1152/ajpheart.00015.2009.

Full text

Abstract:

Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) using neutralizing antibody AFL-4 abrogated FGF-2-mediated limb salvage and blood flow recovery in severely ischemic hindlimb. Interestingly, inhibition of VEGFR3 activity not only diminished lymphangiogenesis, but induced marked dilatation of capillary vessels, showing mural cell dissociation. In these mice, VEGF-C and PDGF-B were upregulated in the later phase after induced ischemia, on day 7, when exogenous FGF-2 expression had already declined, and blockade of VEGFR3 or PDGF-BB activities diminished PDGF-B or VEGF-C expression, respectively. These results clearly indicate that VEGF-C is a critical mediator, not only for lymphangiogenesis, but also for capillary stabilization, the essential molecular mechanism of communication between endothelial cells and mural cells during neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

31

Yokoyama, Yukihiro, Rajiv Baveja, Natalie Sonin, Mark G. Clemens, and Jian X. Zhang. "Hepatic neovascularization after partial portal vein ligation: novel mechanism of chronic regulation of blood flow." American Journal of Physiology-Gastrointestinal and Liver Physiology 280, no. 1 (January 1, 2001): G21—G31. http://dx.doi.org/10.1152/ajpgi.2001.280.1.g21.

Full text

Abstract:

The present study was undertaken to investigate hepatic microcirculatory response following partial portal vein ligation (PPVL) in rats. Portal pressure was markedly increased 2–6 wk after PPVL, but no significant reduction in sinusoidal perfusion and hepatocellular injury were detected. However, marked neovascularization was observed in PPVL rats using intravital microscopy and scanning electron microscopy (SEM). Extremely high red blood cell velocity (2,000–4,900 μm /s) was seen in these vessels. Injection of fluorescein sodium via the carotid artery revealed that the neovessels originated from the hepatic arterial vasculature. This was further confirmed by clamping the common hepatic artery and phenylephrine injection from the carotid artery. These vessels maintained sufficient flow after massive sinusoidal shutdown elicited by the portal infusion of endothelin receptor B agonist IRL-1620. SEM also showed extensive neovascularization at the hilum. Additionally, clamping the portal vein decreased sinusoidal perfusion only by 9.5% in PPVL, whereas a 71.2% decrease was observed in sham. These results strongly suggest that the liver maintains its microcirculatory flow by vascular remodeling from the hepatic arterial vasculature following PPVL.

APA, Harvard, Vancouver, ISO, and other styles

32

Murdoch, Colin E., Markus M. Bachschmid, and Reiko Matsui. "Regulation of neovascularization by S-glutathionylation via the Wnt5a/sFlt-1 pathway." Biochemical Society Transactions 42, no. 6 (November 17, 2014): 1665–70. http://dx.doi.org/10.1042/bst20140213.

Full text

Abstract:

S-glutathionylation occurs when reactive oxygen or nitrogen species react with protein-cysteine thiols. Glutaredoxin-1 (Glrx) is a cytosolic enzyme which enzymatically catalyses the reduction in S-glutathionylation, conferring reversible signalling function to proteins with redox-sensitive thiols. Glrx can regulate vascular hypertrophy and inflammation by regulating the activity of nuclear factor κB (NF-κB) and actin polymerization. Vascular endothelial growth factor (VEGF)-induced endothelial cell (EC) migration is inhibited by Glrx overexpression. In mice overexpressing Glrx, blood flow recovery, exercise function and capillary density were significantly attenuated after hindlimb ischaemia (HLI). Wnt5a and soluble Fms-like tyrosine kinase-1 (sFlt-1) were enhanced in the ischaemic-limb muscle and plasma respectively from Glrx transgenic (TG) mice. A Wnt5a/sFlt-1 pathway had been described in myeloid cells controlling retinal blood vessel development. Interestingly, a Wnt5a/sFlt-1 pathway was found also to play a role in EC to inhibit network formation. S-glutathionylation of NF-κB components inhibits its activation. Up-regulated Glrx stimulated the Wnt5a/sFlt-1 pathway through enhancing NF-κB signalling. These studies show a novel role for Glrx in post-ischaemic neovascularization, which could define a potential target for therapy of impaired angiogenesis in pathological conditions including diabetes.

APA, Harvard, Vancouver, ISO, and other styles

33

Kiel, Christina, Tobias Strunz, Felix Grassmann, and Bernhard H. F. Weber. "Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD)." Cells 9, no. 10 (October 8, 2020): 2257. http://dx.doi.org/10.3390/cells9102257.

Full text

Abstract:

Genome-wide association studies (GWAS) have identified an abundance of genetic loci associated with complex traits and diseases. In contrast, in-depth characterization of an individual genetic signal is rarely available. Here, we focus on the genetic variant rs2168518 in 15q24.1 previously associated with age-related macular degeneration (AMD), but only with suggestive evidence. In a two-step procedure, we initially conducted a series of association analyses to further delineate the association of rs2168518 with AMD but also with other complex phenotypes by using large independent datasets from the International AMD Genomics Consortium (IAMDGC) and the UK Biobank. We then performed a functional annotation with reference to gene expression regulation based on data from the Genotype-Tissue Expression (GTEx) project and RegulomeDB. Association analysis revealed a gender-specific association with male AMD patients and an association predominantly with choroidal neovascularization. Further, the AMD association colocalizes with an association signal of several blood pressure-related phenotypes and with the gene expression regulation of CYP1A1, a member of the cytochrome P450 superfamily of monooxygenases. Functional annotation revealed altered transcription factor (TF) binding sites for gender-specific TFs, including SOX9 and SRY. In conclusion, the pleiotropic 15q24.1 association signal suggests a shared mechanism between blood pressure regulation and choroidal neovascularization with a potential involvement of CYP1A1.

APA, Harvard, Vancouver, ISO, and other styles

34

Alves, C. Henrique, Rosa Fernandes, Ana Raquel Santiago, and António Francisco Ambrósio. "Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration." Cells 9, no. 5 (May 14, 2020): 1217. http://dx.doi.org/10.3390/cells9051217.

Full text

Abstract:

The retina is a highly metabolically active tissue with high-level consumption of nutrients and oxygen. This high metabolic demand requires a properly developed and maintained vascular system. The retina is nourished by two systems: the central retinal artery that supplies the inner retina and the choriocapillaris that supplies the outer retina and retinal pigment epithelium (RPE). Pathological neovascularization, characterized by endothelial cell proliferation and new vessel formation, is a common hallmark in several retinal degenerative diseases, including age-related macular degeneration (AMD). A limited number of studies have suggested that microglia, the resident immune cells of the retina, have an important role not only in the pathology but also in the formation and physiology of the retinal vascular system. Here, we review the current knowledge on microglial interaction with the retinal vascular system under physiological and pathological conditions. To do so, we first highlight the role of microglial cells in the formation and maintenance of the retinal vasculature system. Thereafter, we discuss the molecular signaling mechanisms through which microglial cells contribute to the alterations in retinal and choroidal vasculatures and to the neovascularization in AMD.

APA, Harvard, Vancouver, ISO, and other styles

35

Langer, Harald F., Kyoung-Jin Chung, Valeria V. Orlova, Eun Young Choi, Sunil Kaul, Michael J. Kruhlak, Markella Alatsatianos, et al. "Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis." Blood 116, no. 22 (November 25, 2010): 4395–403. http://dx.doi.org/10.1182/blood-2010-01-261503.

Full text

Abstract:

Abstract Beyond its role in immunity, complement mediates a wide range of functions in the context of morphogenetic or tissue remodeling processes. Angiogenesis is crucial during tissue remodeling in multiple pathologies; however, the knowledge about the regulation of neovascularization by the complement components is scarce. Here we studied the involvement of complement in pathological angiogenesis. Strikingly, we found that mice deficient in the central complement component C3 displayed increased neovascularization in the model of retinopathy of prematurity (ROP) and in the in vivo Matrigel plug assay. In addition, antibody-mediated blockade of C5, treatment with C5aR antagonist, or C5aR deficiency in mice resulted in enhanced pathological retina angiogenesis. While complement did not directly affect angiogenesis-related endothelial cell functions, we found that macrophages mediated the antiangiogenic activity of complement. In particular, C5a-stimulated macrophages were polarized toward an angiogenesis-inhibitory phenotype, including the up-regulated secretion of the antiangiogenic soluble vascular endothelial growth factor receptor-1. Consistently, macrophage depletion in vivo reversed the increased neovascularization associated with C3- or C5aR deficiency. Taken together, complement and in particular the C5a-C5aR axes are potent inhibitors of angiogenesis.

APA, Harvard, Vancouver, ISO, and other styles

36

Donadieu, Emilie, and Catherine M. Riva. "Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice." Ageing Research 3, no. 1 (January 18, 2012): 1. http://dx.doi.org/10.4081/ar.2012.e1.

Full text

Abstract:

Molecular mechanisms underlining hypoxia- induced aged-hearing loss were studied. 3- months C57BL/6 mice were subjected to four weeks of hypoxia (10% 02), whereas, controls were kept under normoxic condition for up to six months. Auditory function was explored by CAP and Preyer’s reflex measurements and correlated with histological analysis of the cochlea. The presence of oxidative damage, HIF-1 responsive target genes regulation involved in cell death, inflammation and neovascularization were assessed by immunofluorescence analysis. Hypoxia was associated to severe hearing loss at 4-8 and 16 KHz and degeneration of the cochlea, with significant cell loss (30%) in the spiral ganglion, the lateral wall, and the hair cells with a basal-apical alteration gradient. This was correlated with ROS formation and HIF-1a overexpression. Cochlear degeneration was due to apoptosis via activated caspase-3, P53, Bax and Bcl-2 protein differential expression in spiral ganglion, modiolus and spiral ligament. On the other hand, Hsp70, NF-kB transcription factor pathway and inflammatory mediators (caspase-1 and TNF-a) were induced in the stria vascularis. Furthermore, a phenomenon of neovascularization was observed with significant thickening of stria vascularis and increased expression of VEGF. In total, we demonstrated that the tandem-HIF-ROS is responsible for the caspase-3 and Bax–mediated apoptosis via P53 protein accumulation in the cochlear neurons, while inflammatory response mediated by Hsp70 stress protein and NF-kB transcription factor generating a neovascularization phenomenon occurred in stria vascularis.

APA, Harvard, Vancouver, ISO, and other styles

37

Matsui, Reiko, Yosuke Watanabe, and Colin E. Murdoch. "Redox regulation of ischemic limb neovascularization – What we have learned from animal studies." Redox Biology 12 (August 2017): 1011–19. http://dx.doi.org/10.1016/j.redox.2017.04.040.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Jakubowski, Aniela, Beth Browning, Matvey Lukashev, Irene Sizing, Jeffrey S. Thompson, Christopher D. Benjamin, Yen-Ming Hsu, Christine Ambrose, Timothy S. Zheng, and Linda C. Burkly. "Dual role for TWEAK in angiogenic regulation." Journal of Cell Science 115, no. 2 (January 15, 2002): 267–74. http://dx.doi.org/10.1242/jcs.115.2.267.

Full text

Abstract:

Angiogenic regulators modulate endothelial cell functions, including proliferation, migration, secretion, and adhesion, through their action on endothelial cells or other cell types. TWEAK, a novel member of the tumor necrosis factor family, appears to be a pro-angiogenic agent on the basis of previous studies demonstrating its ability to induce interleukin-8 production by epithelial tumor lines, stimulate proliferation of human vascular cell types and neovascularization in rat corneas. Here, we further characterized the angiogenic potential of TWEAK, revealing a dual role for TWEAK as an angiogenic regulator. We demonstrate that TWEAK is a potent inducer of endothelial cell survival and cooperates with basic fibroblast growth factor to induce the proliferation and migration of human endothelial cells and morphogenesis of capillary lumens. In contrast, TWEAK antagonizes the morphogenic response of endothelial cells to vascular endothelial growth factor (VEGF) without inhibiting VEGF-induced survival or proliferation. Thus, our observations suggest that TWEAK may differentially regulate microvascular growth, remodeling and/or maintenance in vivo, depending upon the angiogenic context.

APA, Harvard, Vancouver, ISO, and other styles

39

Astrof, Sophie, Denise Crowley, Elizabeth L. George, Tomohiko Fukuda, Kiyotoshi Sekiguchi, Douglas Hanahan, and Richard O. Hynes. "Direct Test of Potential Roles of EIIIA and EIIIB Alternatively Spliced Segments of Fibronectin in Physiological and Tumor Angiogenesis." Molecular and Cellular Biology 24, no. 19 (October 1, 2004): 8662–70. http://dx.doi.org/10.1128/mcb.24.19.8662-8670.2004.

Full text

Abstract:

ABSTRACT Fibronectin splice variants containing the EIIIA and/or EIIIB exons are prominently expressed in the vasculature of a variety of human tumors but not in normal adult tissues. To understand the functions of these splice variants in physiological and tumor angiogenesis, we used EIIIB-null and EIIIA-null strains of mice to examine neovascularization of mouse retinas, pancreatic tumors in Rip-Tag transgenic mice, and transplanted melanomas. Contrary to expectations, physiological and tumor angiogenesis was not significantly affected by the absence of either EIIIA or EIIIB splice variants. Tumor growth was also not affected. In addition, the expression levels of smooth muscle alpha actin, believed to be modulated by EIIIA-containing fibronectins, were not affected either. Our experiments show that despite their tight regulation during angiogenesis, the presence of EIIIA or EIIIB splice variants individually is not essential for neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

40

Chang, Wen-Lung, Pei-Yi Liu, Shu-Lan Yeh, and Huei-Jane Lee. "Effects of Dried Onion Powder and Quercetin on Obesity-Associated Hepatic Menifestation and Retinopathy." International Journal of Molecular Sciences 23, no. 19 (September 21, 2022): 11091. http://dx.doi.org/10.3390/ijms231911091.

Full text

Abstract:

Onion (Allium cepa L.), rich in flavonoids (particularly quercetin), reportedly has anti-obesity properties, but the underlying mechanisms and associated health issues remain unclear. In this study, we compared the effects of dried onion powder (DO) with that of quercetin on high-fat diet (HFD)-induced obesity, nonalcoholic fatty liver disease, and retinal neovascularization. Briefly, rats (n = 9–10 per group) were divided into control, HFD alone (43% fat), HFD + DO (1% DO), HFD + 5DO (5% DO, w/w), and HFD + quercetin (180 mg/kg). After 12 weeks, body fat, markers of metabolism, fatty liver, steatohepatitis, and retinopathy were analyzed. The results revealed that DO and 5DO dose-dependently suppressed body weight, visceral and subcutaneous fat accumulation, and epididymal adipocyte in HFD-fed rats. DO also decreased HFD-induced ALT, AST, free fatty acid, glucose, proinflammatory cytokines, and oxidative stress. DO and 5DO groups had lower triglycerides, total cholesterol, proinflammatory cytokine levels, and ACC-α (a fatty acid synthesis–associated enzyme) expression but higher hepatic antioxidant enzyme activities and fecal lipids. 5DO exhibited better or similar efficacy to quercetin. Both 5DO and quercetin increased fecal levels of acetic acid and butyric acid similarly. They also reduced lipid peroxidation of the eye, retinal adiposity, and neovascularization. However, quercetin resulted in a more apparent decrease in regulation of the Raf/MAPK pathway than DO in eye specimens. Conclusively, DO suppresses visceral, subcutaneous, and liver fat accumulation better than quercetin likely due to higher fecal fat excretion and lower oxidative stress, proinflammatory cytokine levels, and ACC-α expression. Quercetin regulating signal pathways is better than DO at reducing retinal adiposity and neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

41

Carmona, Guillaume, Stephan Göttig, Alessia Orlandi, Jürgen Scheele, Tobias Bäuerle, Manfred Jugold, Fabian Kiessling, et al. "Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis." Blood 113, no. 2 (January 8, 2009): 488–97. http://dx.doi.org/10.1182/blood-2008-02-138438.

Full text

Abstract:

Abstract Ras-associated protein 1 (Rap1), a small GTPase, attracted attention because of its involvement in several aspects of cell adhesion, including integrin- and cadherin-mediated adhesion. Yet, the role of Rap1 genes and of Rap1 effectors for angiogenesis has not been investigated. Human umbilical vein endothelial cells (HUVECs) express Rap1a and Rap1b mRNA. To determine the contribution of Rap1 activity for angiogenesis, we overexpressed Rap1GAP1, a GTPase-activating protein that inhibits Rap1 activity. Overexpression of Rap1GAP1 significantly blocked angiogenic sprouting and tube-forming activity of HUVECs as well as migration and integrin-dependent adhesion. Silencing of Rap1a, Rap1b, or both significantly blocked HUVECs sprouting under basal and basic fibroblast growth factor-stimulated conditions and reduced HUVEC migration and integrin-dependent adhesion. We found that Rap1a and Rap1b are essential for the conformational activation of β1-integrins in endothelial cells. Furthermore, silencing of Rap1a and Rap1b prevented phosphorylation of tyrosine 397 in focal adhesion kinase (FAK) and vascular endothelial growth factor-induced Akt1-activation. Rap1a−/−-deficient and Rap1a+/− heterozygote mice displayed reduced neovascularization after hind limb ischemia compared with wild-type mice. Silencing of RAPL significantly blocked the Rap1-induced sprouting of HUVECs, suggesting that the angiogenic activity of Rap1 is partly mediated by RAPL. Our data demonstrate a critical role of Rap1 in the regulation of β1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization.

APA, Harvard, Vancouver, ISO, and other styles

42

Khmelnitskaya, K. A., A. Y. Gudkova, and E. V. Shlyakhto. "Modern conception about cellular and molecular mechanisms of angiogenesis." Scientific Notes of the I. P. Pavlov St. Petersburg State Medical University 22, no. 1 (March 30, 2015): 6–13. http://dx.doi.org/10.24884/1607-4181-2015-22-1-6-13.

Full text

Abstract:

The review contains modern scientific literary data, recently conducted studies, which devoted to studying of molecular, cellular and genetic mechanisms in processes of angiogenesis. The authors describe in detail angiogenesis stages, value of the main proangiogenic and antiangiogenic factors, apoptosis factors, which have different orientation in regulation of blood vessels development. Role of a special population of bone marrow-derived stem cells - endothelial progenitor cells (EPC) in the neovascularization is analyzed. Participation of VEGF-dependent, ANG/Tie-dependent and Notch-signaling pathways, posttranscription regulation of a genome with participation of microRNA in angiogenesis processes are discussed and reviewed.

APA, Harvard, Vancouver, ISO, and other styles

43

Yang, Mingzhu, Ruiqi Qiu, Weiping Wang, Jingyang Liu, Xiuxiu Jin, Ya Li, Lei Li, and Bo Lei. "P2X7 Receptor Antagonist Attenuates Retinal Inflammation and Neovascularization Induced by Oxidized Low-Density Lipoprotein." Oxidative Medicine and Cellular Longevity 2021 (August 19, 2021): 1–18. http://dx.doi.org/10.1155/2021/5520644.

Full text

Abstract:

Age-related macular degeneration (AMD) is a common and severe blinding disease among people worldwide. Retinal inflammation and neovascularization are two fundamental pathological processes in AMD. Recent studies showed that P2X7 receptor was closely involved in the inflammatory response. Here, we aim to investigate whether A740003, a P2X7 receptor antagonist, could prevent retinal inflammation and neovascularization induced by oxidized low-density lipoprotein (ox-LDL) and explore the underlying mechanisms. ARPE-19 cells and C57BL/6 mice were treated with ox-LDL and A740003 successively for in vitro and in vivo studies. In this research, we found that A740003 suppressed reactive oxygen species (ROS) generation and inhibited the activation of Nod-like receptor pyrin-domain protein 3 (NLRP3) inflammasome and nuclear factor-κB (NF-κB) pathway. A740003 also inhibited the generation of angiogenic factors in ARPE-19 cells and angiogenesis in mice. The inflammatory cytokines and phosphorylation of inhibitor of nuclear factor-κB alpha (IKBα) were repressed by A740003. Besides, ERG assessment showed that retinal functions were remarkably preserved in A740003-treated mice. In summary, our results revealed that the P2X7 receptor antagonist reduced retinal inflammation and neovascularization and protected retinal function. The protective effects were associated with regulation of NLRP3 inflammasome and the NF-κB pathway, as well as inhibition of angiogenic factors.

APA, Harvard, Vancouver, ISO, and other styles

44

Choi, Yoon Kyung, Elaine D. Por, Young-Guen Kwon, and Young-Myeong Kim. "Regulation of ROS Production and Vascular Function by Carbon Monoxide." Oxidative Medicine and Cellular Longevity 2012 (2012): 1–17. http://dx.doi.org/10.1155/2012/794237.

Full text

Abstract:

Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS). CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angiogenesis and mitochondrial biogenesis. Therefore, CO generated either by exogenous delivery or by HO activity can be fundamentally involved in regulating mitochondria-mediated redox cascades for adaptive gene expression and improving blood circulation (i.e., O2delivery) via neovascularization, leading to the regulation of mitochondrial energy metabolism. This paper will highlight the biological effects of CO on ROS generation and cellular redox changes involved in mitochondrial metabolism and angiogenesis. Moreover, cellular mechanisms by which CO is exploited for disease prevention and therapeutic applications will also be discussed.

APA, Harvard, Vancouver, ISO, and other styles

45

BAINBRIDGE, James W. B., Ajay R. MISTRY, Adrian J. THRASHER, and Robin R. ALI. "Gene therapy for ocular angiogenesis." Clinical Science 104, no. 6 (June 1, 2003): 561–75. http://dx.doi.org/10.1042/cs20020314.

Full text

Abstract:

Ocular neovascularization is a central feature of diabetic retinopathy and age-related macular degeneration. These conditions are the major causes of blindness in the developed world. Current treatments are of limited efficacy and associated with significant adverse effects. Characterization of the molecular and cellular events involved in angiogenesis has led to the identification of a number of angiostatic molecules with potential therapeutic value. The systemic administration of small molecule angiostatic proteins risks significant systemic adverse effects and the effect of their intraocular injection is short-lived. Local gene transfer, however, offers the possibility of targeted, sustained and regulatable delivery of angiostatic proteins to the retina after a single procedure to introduce a vector to an intraocular site. The effect of intra-ocular delivery of recombinant viruses carrying genes encoding angiostatic proteins has been demonstrated in rodent models of ocular neovascularization. Recombinant adeno-associated virus-mediated local gene transfer of a vascular endothelial growth factor inhibitor controls both retinal and choroidal neovascularization. The clinical application of this approach may require the means to regulate gene expression in order to minimize the potential for adverse effects. Regulation of transgene expression by means of a hypoxia-responsive promoter offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of ischaemia-induced ocular neovascularization. Preclinical studies of gene transfer in a large animal model following subretinal delivery of a recombinant adeno-associated virus vector have demonstrated efficient sustained reporter gene expression in cells of the outer retina. Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascular disorders.

APA, Harvard, Vancouver, ISO, and other styles

46

Huang, Shuai, Yuanqing Guo, Angela Jacobi, Ziqing Li, Sheng Huang, Jianan He, Xingmo Liu, and Yubo Tang. "Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia." Cellular Physiology and Biochemistry 39, no. 2 (2016): 709–20. http://dx.doi.org/10.1159/000445662.

Full text

Abstract:

Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β) and inhibits the secretion of vascular endothelial growth factor (VEGF). The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs), and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000) by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α) (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001) and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008) were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.

APA, Harvard, Vancouver, ISO, and other styles

47

Min, Xiaojie, Qingjun Zhou, Xiaoguang Dong, Yiqiang Wang, and Lixin Xie. "Retracted: Expression Profile and Regulation of Telomerase Reverse Transcriptase on Oxygen-Induced Retinal Neovascularization." Current Eye Research 36, no. 2 (December 15, 2010): 135–42. http://dx.doi.org/10.3109/02713683.2010.525679.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Husain, Deeba, Rosana D. Meyer, Manisha Mehta, Walther M. Pfeifer, Eva Chou, Gregory Navruzbekov, Ednan Ahmed, and Nader Rahimi. "Role of c-Cbl–Dependent Regulation of Phospholipase Cγ1 Activation in Experimental Choroidal Neovascularization." Investigative Opthalmology & Visual Science 51, no. 12 (December 1, 2010): 6803. http://dx.doi.org/10.1167/iovs.10-5255.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Cochain, C., M. P. Rodero, J. Vilar, A. Recalde, A. L. Richart, C. Loinard, Y. Zouggari, et al. "Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization." Cardiovascular Research 88, no. 1 (May 25, 2010): 186–95. http://dx.doi.org/10.1093/cvr/cvq153.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Wang, Liya, Pingling Shi, Zhongzhong Xu, Jing Li, Yanting Xie, Kenneth Mitton, Kimberly Drenser, and Qi Yan. "Up-Regulation of VEGF by Retinoic Acid During Hyperoxia Prevents Retinal Neovascularization and Retinopathy." Investigative Opthalmology & Visual Science 55, no. 7 (July 14, 2014): 4276. http://dx.doi.org/10.1167/iovs.14-14170.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Neovascularization Regulation'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles