Effect of Aging and Exercise Training on Matrix Metalloproteinases in Rat Heart

Abstract

Aging causes progressive remodeling of the left ventricle including cell loss, turnover of the extracellular matrix (ECM), and fibrosis that contribute to impairment of cardiac function. Matrix metalloproteinases (MMPs) are key enzymes responsible for ECM remodeling, and limited data show age-induced alterations in MMP expression. Recently, our lab. demonstrated that 12 weeks of exercise training ameliorates age-induced remodeling in the aging heart. However, there is a stark paucity of data investigating regulation of MMPs by exercise training in the aging heart. We hypothesized that exercise training would attenuate age-induced changes in MMPs in the left ventricle. PURPOSE: Identify the effects of aging and long-term (12 weeks) exercise training on MMP-1, MMP-2, MMP-3, and MMP-9 protein levels in left ventricle of the rat heart. METHODS: Three and 31 mo. old Fischer 344 × Brown Norway F1 hybrid rats were randomly assigned to young sedentary (YS), young exercise (YE), old sedentary (OS), or old exercise (OE) groups. Exercise training groups ran on a treadmill at 20 m/min (young) or 10 m/min (old), 18% grade, 45 min/day, 5 day/wk for 12 wks. Following training, hearts were extracted in young (6 mo) and old (34 mo) rats and frozen in liquid nitrogen. Pro- and active levels of MMP-1, MMP-2, MMP-3, and MMP-9 were measured in the soluble fractions using Western immunoblot analysis. RESULTS: Pro and active protein levels for MMP-1 and MMP-9 were not altered by aging or exercise training. Active MMP-2 levels significantly decreased (−38%) with aging, but there were no training effects on pro/active MMP-2 levels in old groups. Pro-MMP-3 levels were significantly elevated (+199%) with aging, but an increased trend (+30%, p=0.093) existed in OE compared with OS. CONCLUSION: These data demonstrate that aging significantly decreased active MMP-2 protein levels and increased pro-MMP-3 protein levels, whereas exercise training elevated pro-MMP3 protein levels in the old group. Our findings indicate a differential regulation of MMPs with aging and exercise training in the soluble fractions of heart.