Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8263297 | Experimental Gerontology | 2015 | 40 Pages |
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-Ã). The renin-angiotensin II system (RAS) increases oxidative stress via NADPH oxidase-2 (Nox2) and thus elevates TGF-à 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 Ã 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-à 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.
Related Topics
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Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Yang Lee, Hyo-Bum Kwak, Jeff Hord, Jong-Hee Kim, John M. Lawler,