The protective effect of resveratrol on vascular aging by modulation of the renine-angiotensin system

被引:116
作者
Kim, Eun Nim [1 ]
Kim, Min Young [1 ]
Lim, Ji Hee [1 ]
Kim, Yaeni [1 ,2 ]
Shin, Seok Joon [1 ,2 ]
Park, Cheol Whee [1 ,3 ]
Kim, Yong-Soo [1 ,3 ]
Chang, Yoon Sik [1 ,4 ]
Yoon, Hye Eun [1 ,2 ]
Choi, Bum Soon [1 ,3 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Nephrol, 222 Banpo Daero, Seoul 137701, South Korea
[2] Incheon St Marys Hosp, Dept Internal Med, Incheon, South Korea
[3] Seoul St Marys Hosp, Dept Internal Med, Seoul, South Korea
[4] Yeouido St Marys Hosp, Dept Internal Med, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Aorta; Arterial aging; Inflammation; Oxidative stress; Renine-angiotensin system; Resveratrol; CARDIOVASCULAR-DISEASE ENTERPRISES; PREVENTS RENAL LIPOTOXICITY; PPAR-ALPHA; SUPEROXIDE-DISMUTASE; MAJOR SHAREHOLDERS; MOUSE MODEL; RECEPTOR; SIRT1; ACTIVATION; EXPRESSION;
D O I
10.1016/j.atherosclerosis.2018.01.043
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and aims: This study evaluated the effects of resveratrol on arterial aging and the renin-angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs). Methods: Aging mice were divided into control and resveratrol groups. Histological changes, inflammation, oxidative stress, RAS components, and the expression of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha), and anti-oxidative enzymes was measured in thoracic aortas of 24-month-old mice. The effect of resveratrol on fibrosis, cell senescence, and RAS components was also investigated in VSMCs stimulated by angiotensin (Ang) II. Results: Aorta media thickness, inflammation, fibrosis, and oxidative stress were significantly lower in the resveratrol group than in the control group. Resveratrol treatment decreased serum Ang II level and the aortic expression of prorenin receptor (PRR) and angiotensin converting enzyme (ACE), and increased serum Ang-(1-7) level and the expression of ACE2, Ang II type 2 receptor (AT2R), and Mas receptor (MasR). Resveratrol increased the expression of phosphorylated AMPK, SIRT1, PGC-1 alpha, phosphorylated endothelial nitric oxide synthase and superoxide dismutase 1 and 2, and decreased that of NADPH oxidase 2 and 4. In Ang II-stimulated VSMCs, resveratrol treatment markedly decreased the number of senescence associated beta-galactosidase stained cells and pro-fibrotic protein expression and increased the expression of AT2R and MasR. Conclusions: Resveratrol protects against arterial aging and this effect is associated with reduced activity of the PRReACEeAng II axis and stimulation of the ACE2-Ang-(1-7)-ATR2-MasR axis. (C) 2018 Elsevier B.V. All rights reserved.
引用
收藏
页码:123 / 131
页数:9
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