Sirtuin 1 activation attenuates cardiac fibrosis in a rodent pressure overload model by modifying Smad2/3 transactivation.

ABSTRACT: Aims:Transforming growth factor β1 (TGF-β1) is a prosclerotic cytokine involved in cardiac remodelling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-β signalling by altering its transcriptional activity. Recently, the lysine de-acetylase sirtuin 1 (SIRT1) has been shown to have a cardioprotective effect; however, SIRT1 expression and activity are paradoxically reduced in HF. Herein, we investigate whether pharmacological activation of SIRT1 would induce cardioprotection in a pressure overload model and assess the impact of SIRT1 activation on TGF-β signalling and the fibrotic response. Methods and results:Eight weeks old male C57BL/6 mice were randomized to undergo sham surgery or transverse aortic constricti

SUBMITTER: Bugyei-Twum A 

PROVIDER: S-EPMC6148332 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature