Exercise training attenuates age-dependent elevation of angiotensin II type 1 receptor and Nox2 signaling in the rat heart. Academic Article uri icon


  • 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-). The renin-angiotensin II system (RAS) increases oxidative stress via NADPH oxidase-2 (Nox2) and thus elevates TGF- 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- and fibrosis. Young (3 months, n=20) and old (31 months, n=20) Fischer 344 B rown 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- 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- pathway.

published proceedings

  • Exp Gerontol

altmetric score

  • 4.5

author list (cited authors)

  • Lee, Y., Kwak, H., Hord, J., Kim, J., & Lawler, J. M.

citation count

  • 17

complete list of authors

  • Lee, Yang||Kwak, Hyo-Bum||Hord, Jeff||Kim, Jong-Hee||Lawler, John M

publication date

  • October 2015