Angiotensin II stimulates synthesis of vascular smooth muscle cell proteoglycans with enhanced low density lipoprotein binding properties

Figueroa, Julio E.; Vijayagopal, Parakat

doi:10.1016/s0021-9150(01)00714-6

Cited by 44 publications

(43 citation statements)

References 42 publications

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“…Several in vitro studies demonstrate that angII stimulates proteoglycan synthesis by vascular smooth muscle cells (8,12) as well as by other cell types pertinent to atherosclerosis, including macrophages (45), cardiac myocytes (46), and fibroblasts (34). The mechanism by which angII stimulates proteoglycan synthesis is not fully understood, but it appears to be mediated through the AT1 receptor, although one report suggests that both AT1 and AT2 receptors are involved (12).…”

Section: Discussionmentioning

confidence: 99%

“…The atherogenicity of angII has been ascribed to several effects of angII, including its proinflammatory properties and its effect in stimulating the proliferation of vascular smooth muscle cells (6,7). AngII is known to stimulate the secretion of extracellular matrix (ECM) components by vascular smooth muscle cells, such as laminin, fibronectin, collagen, elastin, and proteoglycans (8)(9)(10)(11)(12). However, it is not known whether this stimulation of ECM components leads to increased LDL retention in the artery wall.…”

mentioning

confidence: 99%

“…Proteoglycans bind lipoproteins via ionic interactions between negatively charged sulfate and carboxylic acid groups on the glycosaminoglycan chains with positively charged residues of apoB in the LDL particle (19,20). Studies have demonstrated that angII stimulates the synthesis of proteoglycans by cultured vascular smooth muscle cells, with one study demonstrating increased LDL binding affinity of proteoglycans synthesized by vascular smooth muscle cells stimulated with angII (8,12). The purpose of this study was to test the hypothesis that one mechanism by which angII induces atherosclerosis is via increased vascular proteoglycan synthesis with increased LDL retention in the artery wall.…”

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Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Huang

Thompson

Wilson

et al. 2008

Journal of Lipid Research

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Angiotensin II (angII) is known to promote atherosclerosis; however, the mechanisms involved are not fully understood. To determine whether angII stimulates proteoglycan production and LDL retention, LDL receptordeficient mice were infused with angII (1,000 ng/kg/min) or saline via osmotic minipumps. To control for the hypertensive effect of angII, a parallel group received norepinephrine (NE; 5.6 mg/kg/day). Arterial lipid accumulation was evaluated by measuring the retention rate of LDL in isolated carotid arteries perfused ex vivo. Mice infused with angII had increased vascular content of biglycan and perlecan and retained twice as much LDL as saline-or NEinfused mice, although no group developed atherosclerosis at this time. To determine whether this increase in biglycan and perlecan content predisposed to atherosclerosis development, mice were infused with angII, saline, or NE for 4 weeks, then pumps were removed and mice received an atherogenic Western diet for another 6 weeks. Mice that had received angII infusions had 3-fold increased atherosclerosis compared with mice that had received saline or NE, and apolipoprotein B colocalized with both proteoglycans. Thus, one mechanism by which angII promotes atherosclerosis is increased proteoglycan synthesis and increased arterial LDL retention, which precedes and contributes to atherosclerosis

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Huang

Thompson

Wilson

et al. 2008

Journal of Lipid Research

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“…31 Losartan abolished the Ang II-induced upregulation of proteoglycans with enhanced LDL-binding properties. 32 Some ARBs activate peroxisome proliferator-activated receptor-g, which regulates lipid metabolism. 33 However, further studies will be needed to establish a relation between ARBs and improved lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of antihypertensive therapy with add-on angiotensin II type 1 receptor blocker after successful coronary stent implantation

et al. 2009

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This study was performed to evaluate the safety and efficacy of additional antihypertensive therapy with angiotensin II type 1 receptor blocker (ARB; olmesartan or valsartan) after successful stent implantation in patients with coronary artery disease (CAD). Fifty patients with CAD after successful stent implantation were included in this study. They were divided into an ARB group, which initially received olmesartan (n¼20, 14±8 mg day À1 ) or valsartan (n¼20, 60±23 mg day À1 ) immediately after stent implantation, and a non-ARB group (n¼10) according to their blood pressure (BP). Follow-up coronary angiography, measurement of BP and blood sampling were performed before (at baseline) and 6-8 months after stent implantation (at follow-up). There were no significant differences in the baseline characteristics between the groups, except for BP. Although there were no changes in % diameter restenosis between the groups, the BP level in the ARB group at follow-up showed a significant reduction (125 ± 12/69 ± 9 mm Hg) and reached the target BP. There were no critical adverse effects in the ARB group throughout the study period. In addition, serum high-sensitive C-reactive protein (hs-CRP) and pentraxin 3 were significantly decreased in the ARB group but not in the non-ARB group. Although olmesartan and valsartan induced similar BP-lowering effects, olmesartan but not valsartan induced a significant decrease in hs-CRP, but did not increase serum uric acid. In conclusion, antihypertensive therapy with add-on low-dose ARB after stent implantation was safe and achieved the target BP. In particular, olmesartan had an anti-inflammatory effect.

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“…Intensive research over the past decade reveals that the actions of angII on atherosclerosis include vascular infl ammation ( 6,7 ), generation of reactive oxygen species ( 8 ), and alterations of endothelial function ( 9 ). AngII was also demonstrated to induce the expression of extracellular matrix (ECM) components in vascular smooth muscle cells (VSMCs), including collagen ( 10 ), laminin ( 11 ), and proteoglycans ( 12 ). However, the mechanisms underlying angII-accelerated atherosclerosis have not been fully elucidated.…”

mentioning

confidence: 99%

Prevention of TGFβ induction attenuates angII-stimulated vascular biglycan and atherosclerosis in Ldlr−/− mice

Tang

Wilson

Thompson

et al. 2013

Journal of Lipid Research

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Journal of Lipid Research Volume 54, 2013 2255(angII) is the major bioactive peptide and effector of RAS and acts via binding to AT1 receptors. Daugherty and Cassis ( 2 ) reported that chronic infusion of angII for 28 days potentiated atherosclerosis in Ldlr Ϫ / Ϫ mice receiving a high-fat diet. RAS blockade has been shown to not only attenuate the progression of atherosclerotic lesions in animals ( 3 ), but also has emerged as a therapy for human cardiovascular diseases ( 4, 5 ). Intensive research over the past decade reveals that the actions of angII on atherosclerosis include vascular infl ammation ( 6, 7 ), generation of reactive oxygen species ( 8 ), and alterations of endothelial function ( 9 ). AngII was also demonstrated to induce the expression of extracellular matrix (ECM) components in vascular smooth muscle cells (VSMCs), including collagen ( 10 ), laminin ( 11 ), and proteoglycans ( 12 ). However, the mechanisms underlying angII-accelerated atherosclerosis have not been fully elucidated.The "response to retention hypothesis" proposes that the subendothelial retention of the atherosclerotic lipoproteins (e.g., apoB-containing LDL) by ECM molecules such as proteoglycans via electrostatic attraction contributes to the initiation of atherosclerosis development ( 13,14 ). Biglycan is a member of chondroitin sulfate/dermatan sulfate containing small leucine-rich proteoglycans and binds apoB-containing lipoproteins ( 15 ). Biglycan was shown to be the proteoglycan most colocalized with apoB in both human and mouse atherosclerosis ( 16-18 ). Overexpression of human Bgn by rat smooth muscle cells (SMCs) results in increased lipoprotein binding on ECM Abstract Angiotensin II (angII) accelerates atherosclerosis, but the mechanisms are not fully understood. The aim of this study was to determine whether TGF ␤ is required for angIIinduced atherosclerosis. Ldlr -null mice fed a normal chow diet were infused with angII or saline for 28 days. A single injection of TGF ␤ neutralizing antibody 1D11 (2 mg/kg) prevented angII-induction of TGF ␤ 1 levels, and strikingly attenuated angII-induced accumulation of aortic biglycan content. To study atherosclerosis, mice were infused with angII or saline for 4 weeks, and then fed Western diet for a further 6 weeks. 1D11 had no effect on systolic blood pressure or plasma cholesterol; however, angII-infused mice that received 1D11 had reduced atherosclerotic lesion area by 30% ( P < 0.05). Immunohistochemical analyses demonstrated that angII induced both lipid retention and accumulation of biglycan and perlecan which colocalized with apoB. 1D11 strikingly reduced the effect of angII on biglycan but not perlecan. 1D11 decreased total collagen content ( P < 0.05) in the lesion area without changing plaque infl ammation markers (CD68 and CD45). Thus, this study demonstrates that neutralization of TGF ␤ attenuated angII stimulation of biglycan accumulation and atherogenesis in mice, suggesting that TGF ␤ -mediated biglycan induction is one of the mechanisms underlying angII-promot...

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Angiotensin II stimulates synthesis of vascular smooth muscle cell proteoglycans with enhanced low density lipoprotein binding properties

Cited by 44 publications

References 42 publications

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Safety and efficacy of antihypertensive therapy with add-on angiotensin II type 1 receptor blocker after successful coronary stent implantation

Prevention of TGFβ induction attenuates angII-stimulated vascular biglycan and atherosclerosis in Ldlr−/− mice

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