Eun Nim Kim1, Min Young Kim1, Ji Hee Lim1, Yaeni Kim2, Seok Joon Shin2, Cheol Whee Park3, Yong-Soo Kim3, Yoon Sik Chang4, Hye Eun Yoon5, Bum Soon Choi6. 1. Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Republic of Korea. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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.
Abstract
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-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. 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-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. 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.
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-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. 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-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. 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.
Authors: Vanessa Dela Justina; Jéssica S G Miguez; Fernanda Priviero; Jennifer C Sullivan; Fernanda R Giachini; R Clinton Webb Journal: Front Aging Date: 2021-09-10