Angiotensin-ll-lnduced Angiogenesis in Sponge Implants in Mice

Andrade, Sílvia Passos; Cardoso, Cibele C.; Machado, R. D. P.; Beraldo, W. T.

doi:10.1159/000179189

Cited by 36 publications

(17 citation statements)

References 10 publications

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“…13,20 Arteriosclerotic lesions exhibit increased formation of microvessels within the adventitia and the hyperplastic media. Therefore, we examined protein expression of ACE, Ang II, and CYR61 within capillaries and small blood vessels in lesion areas.…”

Section: Colocalization Of Ang II and Cyr61 In Microvessels Of Human mentioning

confidence: 99%

Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II

et al. 2002

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Background-The renin-angiotensin system is thought to be involved in development and progression of arteriosclerosis, thereby contributing to adverse cardiovascular events. To elucidate the role of angiotensin II (Ang II) at a cellular level, we analyzed the Ang II-induced gene expression profile. Methods and Results-Genes induced on Ang II stimulation (10 Ϫ7 mol/L, 45 minutes) in rat smooth muscle cells were analyzed by polymerase chain reaction selected subtraction. In addition to known genes, such as interleukin 6, leukemia inhibitory factor, and c-fos, we identified CYR61, an angiogenic immediate early gene. Northern blot analysis revealed a rapid 2.5-fold increase of CYR61 transcript levels by Ang II, peaking at 30 minutes, which was blunted by Ang II type 1 receptor blockade. Exposure of rat aortic rings to Ang II (30 minutes) revealed a 2-fold, and intraperitoneal injection of Ang II (30 minutes) in mice a 3-fold, increase of aortic CYR61 transcripts. In arteriosclerotic aortas of apolipoprotein E-deficient mice, CYR61 transcripts confirmed by in situ hybridization and proteins shown by immunohistochemistry were elevated, whereas they were hardly detectable in wild types. In human carotid atherectomies and arteriosclerotic coronary arteries, immunohistochemical analysis revealed expression of CYR61 within connective tissue in neointima, adventitia, and surrounding small capillaries and blood vessels, colocalized with ACE and Ang II. Normal human arteries showed no significant staining for CYR61. Conclusions-CYR61, an angiogenic factor, is induced by Ang II in vascular cells and tissue. The expression of CYR61, colocalized with Ang II and ACE, in small vessels of human arteriosclerotic lesions is consistent with the notion that the activated renin-angiotensin system may contribute to plaque neovascularization by enhancing regulators of microvessel formation and cell proliferation.

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Section: Colocalization Of Ang II and Cyr61 In Microvessels Of Human mentioning

confidence: 99%

Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II

et al. 2002

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“…[10][11][12][13] Other studies have also investigated the angiogenic effects of exogenous AII in vivo angiogenesis models. [14][15][16][17] Furthermore, recent studies have revealed local expression of several components of the RAS in various cancer cells and tissues. 18 A large-scale clinical trial for hypertension demonstrated that inhibitors of angiotensin-converting enzyme (ACE) reduced mortality rates not only of those due to cardiovascular diseases but also those due to malignant tumors.…”

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Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis

Imai

Hashimoto

Kihara

et al. 2007

Laboratory Investigation

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Angiotensin II (AII) is a multifunctional bioactive peptide, and host renin-angiotensin system (RAS) is closely associated with tumor growth. Recent reports have described that AII is a proangiogenic growth factor, and that Angiotensin II type 1 (AT1) receptor antagonists reduce tumor growth and tumor-associated angiogenesis. In this paper, we investigated the participation of AT1 receptor-signaling in cancer progression using murine Lewis lung carcinoma (LLC) cells, which express AT1 receptor, and AT1a receptor gene-deficient (AT1aÀ/À) mice. When LLC cells were implanted subcutaneously into wild-type (WT) mice, developed tumors showed intensive angiogenesis with an induction of vascular endothelial growth factor (VEGF) a. Compared with WT mice, tumor growth and tumor-associated angiogenesis was reduced in AT1aÀ/À mice with reduced expression of VEGFa. In AT1aÀ/À mice, administration of the AT1 receptor antagonist, TCV-116, showed further reductions of tumor growth, tumor-associated angiogenesis, and VEGFa expression. In vitro study, the expression of VEGFa mRNA and the production of VEGFa protein in LLC cells were significantly increased by AII, which were cancelled by AT1 receptor antagonist, CV-11974. Although the expression of other angiogenic factors, such as angiopoietin-1, angiopoietin-2, epidermal growth factor, and VEGF receptor 2 mRNA, was also investigated in tumor tissues, the expression of VEGFa was most correlated with tumor size among those other angiogenic factors. VEGFa induction by AT1 receptor-signaling in both host and tumor tissues is one of key regulators of tumor growth and tumor-associated angiogenesis. In conclusion, tumor tissue RAS as well as host tissue RAS were found to have an important role in tumor growth. AT1 receptor-signaling blockade may be a novel and effective target in the treatment of cancer. The renin-angiotensin system (RAS) plays important roles in the regulation of cardiovascular homeostasis and blood pressure. 1 Many pathophysiological activities of angiotensin II (AII) are known to be mediated by the seven transmembrane receptors. Two major subtypes of AII receptors, namely AT1 receptor and AT2 receptor, have been identified, with the former having receptor subtypes, AT1a and AT1b. 2 Most of AII functions in the cardiovascular system are mediated through the AT1 receptor, and in rodents they are mediated through the AT1a receptor. [3][4][5][6] Recently, many reports have suggested that AII is involved in other functions, such as apoptosis, vascular remodeling, and inflammation. 7-9 As regards vascular remodeling, several studies have shown that AII promotes proliferation, migration, and growth factor synthesis in several types of vascular cells, including smooth muscle cells and pericytes. [10][11][12][13] Other studies have also investigated the angiogenic effects of exogenous AII in vivo angiogenesis models. 14-17 Furthermore, recent studies have revealed local expression of several components of the RAS in various cancer cells and tissues. 18 A large-scale clinica...

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“…Angiotensin II (Ang II), a major participant in the RAAS, was initially described as a vasoconstrictor, but recent studies have revealed that it also participates in cell growth, cell differentiation and apoptosis (Stoll et al, 1995;Escobar et al, 2004), and has a role in cell migration and conformation of the extracellular matrix (Coker et al, 2001). Some reports indicate that Ang II induce neovascularisation (Fernandez et al, 1985;Le Noble et al, 1991;Andrade et al, 1996) due to stimulation of growth factors, such as platelet-derived growth factor (PDGF) (Khachigian et al, 2000;Cook et al, 2002), transforming growth factor beta b (TGFb) (Kagami et al, 1994;Ohta et al, 1994;Hamaguchi et al, 1999;Weigert et al, 2002), insulin-like growth factor 1 (IGF-1) (Brink et al, 1999;Haddad et al, 2003), basic fibroblast growth factor (bFGF) (Peng et al, 2001), vascular endothelial growth factor (VEGF) (Otani et al, 1998;Tamarat et al, 2002) and angiopoietin 2 (Otani et al, 2001). Angiotensin II also induces the expression of proto-oncogenes in smooth vascular muscle cells, including c-fos, c-jun, c-myc, erg-1, VL-30, and the activator of the protein 1 complex (Cook et al, 2002), Interestingly, many of these effects are inhibited by the blockage of the AT 1 receptor (Fujiyama et al, 2001).…”

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Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

et al. 2005

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Angiotensin II (Ang II) is a main effector peptide in the renin -angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT 1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT 1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg À1 to rats with C6 glioma significantly decreased tumoral volume and production of plateletderived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dosedependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT 1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis.

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Angiotensin-ll-lnduced Angiogenesis in Sponge Implants in Mice

Cited by 36 publications

References 10 publications

Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II

Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II

Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis

Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

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