Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea; Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea.
Atherosclerosis. 2018 Mar;270:123-131. doi: 10.1016/j.atherosclerosis.2018.01.043. Epub 2018 Feb 2.
This study evaluated the effects of resveratrol on arterial aging and the renin-angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs).
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-γ co-activator 1α (PGC-1α), 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.
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-1α, 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 β-galactosidase stained cells and pro-fibrotic protein expression and increased the expression of AT2R and MasR.
Resveratrol protects against arterial aging and this effect is associated with reduced activity of the PRR-ACE-Ang II axis and stimulation of the ACE2-Ang-(1-7)-ATR2-MasR axis.
本研究评估了白藜芦醇对小鼠动脉老化和肾素-血管紧张素系统（RAS）的影响，以及对血管平滑肌细胞（VSMCs）的影响。
将衰老小鼠分为对照组和白藜芦醇组。在 24 个月大的小鼠的胸主动脉中测量组织学变化、炎症、氧化应激、RAS 成分以及 AMP 激活蛋白激酶（AMPK）、沉默信息调节因子 T1（SIRT1）、过氧化物酶体增殖物激活受体-γ 共激活因子 1α（PGC-1α）和抗氧化酶的表达。还研究了白藜芦醇对血管紧张素（Ang）II 刺激的 VSMCs 纤维化、细胞衰老和 RAS 成分的影响。
白藜芦醇组的主动脉中层厚度、炎症、纤维化和氧化应激明显低于对照组。白藜芦醇治疗降低了血清 Ang II 水平和主动脉原肾素受体（PRR）和血管紧张素转换酶（ACE）的表达，增加了血清 Ang-（1-7）水平和 ACE2、血管紧张素 II 型 2 受体（AT2R）和 Mas 受体（MasR）的表达。白藜芦醇增加了磷酸化 AMPK、SIRT1、PGC-1α、磷酸化内皮型一氧化氮合酶和超氧化物歧化酶 1 和 2 的表达，降低了 NADPH 氧化酶 2 和 4 的表达。在 Ang II 刺激的 VSMCs 中，白藜芦醇治疗显著减少了衰老相关的β-半乳糖苷酶染色细胞的数量和促纤维化蛋白的表达，并增加了 AT2R 和 MasR 的表达。
白藜芦醇可预防动脉老化，这种作用与降低 PRR-ACE-Ang II 轴的活性和刺激 ACE2-Ang-（1-7）-ATR2-MasR 轴有关。
