Exercise Training Attenuates Age-dependent Elevation of Angiotensin II Type 1 Receptor and Nox2 Signaling in the Rat Heart

Title
Exercise Training Attenuates Age-dependent Elevation of Angiotensin II Type 1 Receptor and Nox2 Signaling in the Rat Heart
Authors
곽효범
Keywords
Heart, Angiotensin II receptor 1, Aging, NADPH oxidase, TGF-beta
Issue Date
2015-10
Publisher
EXPERIMENTAL GERONTOLOGY
Series/Report no.
EXPERIMENTAL GERONTOLOGY ; Vol70 Startpage 163 Endpage 173
Abstract
Fibrosis of the aging heart impedes cardiac function and increases the risk of arrhythmias and heart disease. Previously, we demonstrated that exercise-induced reduction of collagen I in the aging heart was linked to a suppression of oxidative stress and transforming growth factor-beta (TGF-ß). The renin–angiotensin II system (RAS) increases oxidative stress via NADPH oxidase-2 (Nox2) and thus elevates TGF-ß and collagen accumulation. Therefore, we tested the hypothesis that exercise training would alleviate age-related upregulation of the angiotensin II receptor I (AT1R) and NADPH oxidase-2 (Nox2), concomitant with suppression of TGF-β and fibrosis. Young (3 months, n = 20) and old (31 months, n = 20) Fischer 344 × Brown Norway F1 (FBNF1) hybrid rats were assigned into sedentary and exercise groups, with exercise training rats training on a treadmill 45 min/day, 5 days/week for the next 12 weeks. Exercise training mitigated age-related upregulation of AT1R, Nox2 activity, and Nox2 subunits gp91phox and p47phox. Exercise training also attenuated TGF-ß positive staining and downstream effectors of fibrosis in the aging heart: connective tissue growth factor, phosphorylation of Smad2 at Ser423, myofibroblast proliferation, and collagen I-positive staining. Our results are consistent with the hypothesis that exercise training protects against age-dependent cardiac fibrosis by suppressing AT1R and Nox2 as part of a RAS–Nox2–TGF-β pathway.
URI
https://www.sciencedirect.com/science/article/pii/S0531556515300231
http://dspace.inha.ac.kr/handle/10505/55565
ISSN
0531-5565
Appears in Collections:
School of Arts & Sports(예술체육학부) > Kinesiology (스포츠과학) > Journal Papers (스포츠과학_학술논문)
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