Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Viswanathan, Mohan; Strömberg, Christer; Seltzer, Alicia; Saavedra, Juan M.

doi:10.1172/jci116043

Cited by 150 publications

(74 citation statements)

References 36 publications

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“…Ang II receptor expression has been demonstrated in the neointima of experimentally injured vessels 8 and vascular smooth muscle cells of human atherosclerotic plaques. 6 The critical role of tissue Ang II receptor expression and activation in the pathobiology of intimal hyperplasia is supported by the observation of prevention of neointimal hyperplasia in response to vascular injury and atherosclerosis by ACE inhibitors and AT 1 receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…6 Rakugi et al 7 demonstrated induction of the angiotensinconverting enzyme (ACE) in the neointima of injured blood vessels and speculated on its possible role in restenosis after angioplasty. Viswanathan et al 8 described increased Ang II receptor expression in the neointima after vascular injury, which would facilitate the action of Ang II. ACE has also been found in vascular smooth muscle cells in intimal lesions and in macrophages and vascular smooth muscle cells in the fibroproliferative lesion of human atherosclerotic plaques from atherectomy, surgical, and postmortem specimens.…”

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confidence: 99%

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Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

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Abstract-Angiotensin II (Ang II) promotes vascular smooth muscle growth and may be involved in the initiation and progression of atherosclerosis. To examine whether Ang II receptor expression in vascular tissues is altered in atherosclerosis, male New Zealand White rabbits were fed a high-cholesterol diet (1% cholesterolϩ4% coconut oil mixed with regular chow; hypercholesterolemic group, nϭ12) or regular chow (control group, nϭ8) for 10 weeks. At the end of this period, the serum cholesterol level in the rabbits fed the high-cholesterol diet was higher than that in the control group (3616Ϯ144 versus 30Ϯ1 mg/dL, PϽ0.001). There was no atherosclerosis in the aortas of the control group, whereas 51Ϯ6% of the aorta was covered with atherosclerosis in the hypercholesterolemic group. Total Ang II receptor expression in the atherosclerotic aortic tissues was increased 5-fold in the hypercholesterolemic rabbits (292Ϯ28 versus 51Ϯ32 fmol/mg tissue, meanϮSE, PϽ0.001), and the increased Ang II receptor expression was entirely due to enhanced Ang II type 1 (AT 1 ) receptor expression (289Ϯ38 versus 38Ϯ18 fmol/mg, PϽ0.001), as Ang II type 2 receptor expression was unaltered (7Ϯ5 versus 3Ϯ2 fmol/mg, PϭNS). AT 1 receptors were localized primarily in the media and to some extent in the intima of the atherosclerotic aorta, as determined by immunohistochemistry with specific monoclonal and polyclonal AT 1 receptor antibodies. Increased synthesis of AT 1 receptor mRNA in atherosclerotic tissues was confirmed by reverse transcription-polymerase chain reaction. To evaluate the functional significance of increased AT 1 receptor expression, the constrictor response of aortic rings to Ang II was examined and found to be markedly enhanced in atherosclerotic aortic rings (PϽ0.01 versus control aortic rings). The endotheliumdependent relaxation of aortic rings from hypercholesterolemic rabbits was markedly attenuated (PϽ0.001). This study shows that hypercholesterolemia in rabbits results in atherosclerosis, loss of endothelium-dependent relaxation, and increased Ang II receptor (entirely AT 1 receptor) expression in aortic tissues, which may result in altered vasoreactivity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Yang

Phillips

Mohuczy

et al. 1998

ATVB

121

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“…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][8][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.…”

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confidence: 99%

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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“…In injured arteries, components of renin-angiotensin system are upregulated, such as renin, 8 angiotensinogen, 9 ACE, 10,11 and Ang II receptors. 12,13 We have developed a mouse model of vascular disease induced by polyethylene cuff placement around the femoral artery, in which ACE and the AT 1 receptor are upregulated, followed by neointimal thickening. 13 Estrogen replacement therapy suppresses the prevalence of cardiovascular disease in postmenopausal women 14 and reduces plasma LDL cholesterol and increases HDL cholesterol levels.…”

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confidence: 99%

Effect of Estrogen and AT ₁ Receptor Blocker on Neointima Formation

et al. 2002

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Abstract-The present study explored the possibility that estrogen may enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT 1 ) receptor blocker on neointima formation in vascular injury, and investigated the signaling mechanism involved in their actions. Polyethylene cuff placement around the femoral artery of mice induced neointima formation and increased bromodeoxyuridine (BrdU) incorporation into vascular smooth muscle cells. These changes were significantly smaller in female mice than in male mice. Ovariectomy enhanced neointima formation and BrdU incorporation in the injured artery, which were reversed by 17␤-estradiol (80 g/kg per day) replacement. Treatment with a selective AT 1 receptor blocker, olmesartan (3 mg/kg per day), significantly inhibited neointima formation and BrdU incorporation, whereas the inhibitory effects of olmesartan were more marked in intact female mice than in male or ovariectomized mice. Phosphorylation of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription (STAT) 1, and STAT3 was increased in the injured artery. These increases were significantly smaller in intact female mice than in male or ovariectomized mice. Olmesartan or estrogen attenuated the phosphorylation of ERK and STAT in the injured artery, whereas these inhibitory effects were greater in intact female mice. Lower doses of olmesartan (0.5 mg/kg per day) or 17␤-estradiol (20 g/kg per day) did not influence neointima formation, BrdU incorporation, and ERK and STAT phosphorylation in ovariectomized mice, whereas coadministration of olmesartan and 17␤-estradiol at these doses attenuated these parameters. These results indicate that estrogen and an AT 1 receptor blocker synergistically attenuate vascular remodeling, which is at least partly via inhibition of ERK and STAT activity.

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Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Abstract: Clin. Invest. 1992.90:1707-1712

Cited by 150 publications

References 36 publications

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

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

Effect of Estrogen and AT ₁ Receptor Blocker on Neointima Formation

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Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Abstract: Clin. Invest. 1992.90:1707-1712

Cited by 150 publications

References 36 publications

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits

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

Effect of Estrogen and AT 1 Receptor Blocker on Neointima Formation

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Effect of Estrogen and AT ₁ Receptor Blocker on Neointima Formation