The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE−/− mice through inhibiting vascular inflammatory response

Chen, Yi xi; Zhang, Man; Cai, Yujun; Zhao, Qian; Dai, Wenjian

doi:10.1016/j.bbrc.2015.08.066

Cited by 47 publications

(36 citation statements)

References 28 publications

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“…SIRT1 deacetylates RelA/p65 at K310 and suppresses its binding to naked DNA in human aortic endothelial cells; subsequently this interferes with NF-κB signal activation, thereby preventing the expression of genes responsible for synthesis of adhesion molecules, VCAM-1 and ICAM-1 (8,42). Furthermore, previously described NF-κB signaling pathway suppression by SIRT1 contributes to inhibition of pro-inflammatory cytokine synthesis, including TNF-α, IL-1β, IL-6 and MCP-1 (6). SIRT1 activation may also suppress angiotensin II type I receptor expression in VSMCs contributing to the mechanism by preventing the increase of blood pressure and vessel contraction (43).…”

Section: Discussionmentioning

confidence: 92%

“…Sirtuin-1 (SIRT1), adiponectin and calprotectin (S100A8/A9) are characterized as factors able to modulate either the NF-κB signaling pathway or toll-like receptor 4 (TLR-4) (6-9). Furthermore, they are considered to be important elements for the molecular pathogenesis of atherosclerosis (4)(5)(6)10,11). SIRT1 is highly expressed in endothelial cells where it controls angiogenesis through a broad variety of transcriptional regulators, including p53, fork-head box O (FoxO), NF-κB, promyelocytic leukemia protein and activated receptor-γ.…”

Section: Introductionmentioning

confidence: 99%

“…SIRT1 serves a crucial role in endothelial homeostasis and it is suggested that overexpression of SIRT1 may contribute to vasoprotection (12,13). In a previous experimental study, it was demonstrated that activation of SIRT1 is associated with a reduction in atherosclerotic lesion macrophage content, as well as atherosclerotic lesion size in aortic arches (6). Furthermore, SIRT1 transgenic apolipoprotein E null (apoE −/− ) mice had fewer atherosclerotic lesions, indicating that endothelium-specific SIRT1 overexpression may suppress atherogenesis by influencing endothelial cell survival and function, mediated through regulating the level of nitric oxide synthase (NOS)-3 (14).…”

Section: Introductionmentioning

confidence: 99%

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Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

Wiciński

Malinowski

Węclewicz

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Resveratrol (3, 4', 5-trihydroxy-trans-stilbene) is a natural, non-flavonoid polyphenol that exerts protective properties against atherosclerosis-associated endothelial dysfunction and senescence. The present study aimed to assess the influence of resveratrol on vascular contractility and molecular factors including sirtuin-1 (SIRT1), adiponectin and calprotectin (S100A8/A9) that are considered to be important elements of atherogenesis. A total of 17 male rats were divided into a control and treatment group and administered resveratrol or a placebo. Pharmacometrics were performed on an isolated and perfused tail artery. Serum SIRT1, adiponectin and S100A8/A9 levels were quantified using an ELISA assay. The level of SIRT1 in the control and treatment groups at time 0 was 4.26 and 4.45 ng/ml, respectively. SIRT1 in the control and treatment groups following 2 weeks of treatment was 4.59 and 6.86 ng/ml, respectively (P<0.05) and following 4 weeks of treatment was 4.15 and 6.38 ng/ml, respectively (P<0.05). The level of adiponectin in the control and treatment groups at time 0 was 1.24 and 1.21 ng/ml, respectively. Following 2 weeks of treatment, the level of adiponectin in the control and treatment groups was 1.22 and 1.2 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 1.26 and 1.58 ng/ml, respectively (P<0.05). The S100A8/A9 level in control and treatment groups at time 0 was 0.39 and 0.33 ng/ml, respectively. The level of S100A8/A9 in control and treatment groups following 2 weeks of treatment was 0.37 and 0.35 ng/ml, respectively (P>0.05) and following 4 weeks of treatment was 0.34 and 0.32 ng/ml, respectively (P>0.05). EC 50 values obtained for phenylephrine in resveratrol-pretreated arteries were significantly higher than controls in the presence and absence of A7-hydrochloride (P<0.05). The results of the present study indicate a significant increase in the concentration of SIRT1 and adiponectin in the resveratrol-pretreated group (P<0.05). S100A8/A9 serum concentrations remained unchanged. Reactivity of resistant arteries was significantly reduced for resveratrol-pretreated vessels and this effect was partially independent of phosphodiesterase (PDE1). Additionally, there was a synergistic interaction observed between resveratrol and the PDE1 inhibitor.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

Wiciński

Malinowski

Węclewicz

et al. 2017

Experimental and Therapeutic Medicine

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“…155 SRT1720 possesses also anti-atherogenic activity. 156 The polyphenol S17834, which up-regulates SIRT1, has similar anti-inflammatory and anti-atherogenic actions and exerts cardioprotection in mice with accelerated CV aging phenotypes. 157–159 …”

Section: Potential Interventions That Retard Cardiovascular Agingmentioning

confidence: 99%

Pharmacological Strategies to Retard Cardiovascular Aging

Alfaras

Germanio

Bernier

et al. 2016

Circulation Research

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Aging is the major risk factor for cardiovascular diseases (CVD), which are the leading cause of death in the United States. Traditionally, the effort to prevent CVD has been focused on addressing the conventional risk factors, including hypertension, hyperglycemia, hypercholesterolemia, and high circulating levels of triglycerides. However, recent preclinical studies have identified new approaches to combat CVD. Calorie restriction has been reproducibly shown to prolong lifespan in various experimental model animals. This has led to the development of calorie restriction mimetics and other pharmacological interventions capable to delay age-related diseases. In this review, we will address the mechanistic effects of aging per se on the cardiovascular system and focus on the pro-longevity benefits of various therapeutic strategies that support cardiovascular health.

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“…Recently, inflammatory actions of Ang II were diminished by sirtuin-1 (SIRT-1) activator SRT1720. Treatment with SRT1720 decreased expression of TNF-a, IL-6, MCP-1, VCAM-1, ICAM-1, activation of NF-kB, STAT3 and infiltration of inflammatory cells in atherosclerotic plaques, induced by Ang II [67]. In order to inhibit Ang II signaling, SIRT-1 activation is a promising atheroprotective mechanism.…”

Section: Role Of Ras In Atherosclerosis Developmentmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

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The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

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The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE−/− mice through inhibiting vascular inflammatory response

Cited by 47 publications

References 28 publications

Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

Pharmacological Strategies to Retard Cardiovascular Aging

Involvement of the Renin‐Angiotensin System in Atherosclerosis

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