PMID- 29407880 OWN - NLM STAT- MEDLINE DCOM- 20190528 LR - 20190528 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 270 DP - 2018 Mar TI - The protective effect of resveratrol on vascular aging by modulation of the renin-angiotensin system. PG - 123-131 LID - S0021-9150(18)30043-1 [pii] LID - 10.1016/j.atherosclerosis.2018.01.043 [doi] AB - 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 1alpha (PGC-1alpha), 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-1alpha, 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 PRR-ACE-Ang II axis and stimulation of the ACE2-Ang-(1-7)-ATR2-MasR axis. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Kim, Eun Nim AU - Kim EN AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea. FAU - Kim, Min Young AU - Kim MY AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea. FAU - Lim, Ji Hee AU - Lim JH AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea. FAU - Kim, Yaeni AU - Kim Y AD - 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. FAU - Shin, Seok Joon AU - Shin SJ AD - 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. FAU - Park, Cheol Whee AU - Park CW AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea. FAU - Kim, Yong-Soo AU - Kim YS AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea. FAU - Chang, Yoon Sik AU - Chang YS AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea; Department of Internal Medicine, Yeouido St. Mary's Hospital, Seoul, Republic of Korea. FAU - Yoon, Hye Eun AU - Yoon HE AD - 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. Electronic address: berrynana@catholic.ac.kr. FAU - Choi, Bum Soon AU - Choi BS AD - Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea. Electronic address: sooncb@catholic.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180202 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (PPAR alpha) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppara protein, mouse) RN - 0 (Ppargc1a protein, mouse) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Age Factors MH - Aging MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*pharmacology MH - Aorta, Thoracic/drug effects/metabolism/pathology MH - Cells, Cultured MH - Cellular Senescence/*drug effects MH - Fibrosis MH - Gene Expression Regulation MH - Male MH - Mice, Inbred C57BL MH - Muscle, Smooth, Vascular/*drug effects/metabolism/pathology MH - Myocytes, Smooth Muscle/*drug effects/metabolism/pathology MH - Oxidative Stress/drug effects MH - PPAR alpha/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism MH - Renin-Angiotensin System/*drug effects/genetics MH - Resveratrol/*pharmacology MH - Signal Transduction/drug effects MH - Sirtuin 1/metabolism OTO - NOTNLM OT - Aorta OT - Arterial aging OT - Inflammation OT - Oxidative stress OT - Renin-angiotensin system OT - Resveratrol EDAT- 2018/02/07 06:00 MHDA- 2019/05/29 06:00 CRDT- 2018/02/07 06:00 PHST- 2017/09/11 00:00 [received] PHST- 2017/12/18 00:00 [revised] PHST- 2018/01/24 00:00 [accepted] PHST- 2018/02/07 06:00 [pubmed] PHST- 2019/05/29 06:00 [medline] PHST- 2018/02/07 06:00 [entrez] AID - S0021-9150(18)30043-1 [pii] AID - 10.1016/j.atherosclerosis.2018.01.043 [doi] PST - ppublish SO - Atherosclerosis. 2018 Mar;270:123-131. doi: 10.1016/j.atherosclerosis.2018.01.043. Epub 2018 Feb 2.