期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 308, 期 5, 页码 H424-H434出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00454.2014
关键词
resveratrol; fibrosis; cardiac function; sirtuin 3; transforming growth factor-beta; mothers against decapentaplegic homolog 3
资金
- National 973 Basic Research Program of China [2012CB722406]
- National Natural Science Foundation of China [81070076]
Sirtuins [sirtuin (SIRT) 1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli. However, this protective effect was not observed in SIRT3 knockout mice. Additionally, the activation of SIRT3 by RSV ameliorated collagen deposition and improved cardiac function. In isolated cardiac fibroblasts, pretreatment with RSV suppressed fibroblast-to-myoblast transformation by inhibiting the transforming growth factor-beta/Smad3 pathway. Therefore, these data indicate that the activation of SIRT3 by RSV could ameliorate cardiac fibrosis and improve cardiac function via the transforming growth factor-beta/Smad3 pathway.
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