Inhibition of Src improves cardiac fibrosis in AngII-induced hypertrophy by regulating the expression of galectin-3.

Abstract

The expression of Src is upregulated in the vasculature associated with cardiac hypertrophy events. Here, we aimed to explore the underlying mechanism of Src in angiotensin II (AngII)-mediated cardiac fibrosis and hypertrophy. The heart conditional Src knockout mouse model was established and administrated with AngII. The effects of Src on the AngII-mediated cardiac hypertrophy were assessed by Hematoxylin and Eosin (HE), Masson's trichrome, immunohistochemical staining, Annexin V-FITC/PI apoptosis detection assay and Western blot analysis. The expression levels of galectin-3, Src and the hypertrophy marker brain natriuretic peptide (BNP), as well as the phosphorylation of Src were all elevated in heart tissues of mice with AngII-induced cardiac hypertrophy and fibrosis. Heart conditional Src knockout attenuated AngII-activated cardiac fibrosis and hypertrophy in mice. Consistently, AngII could promote the expression of Src in a dose-dependent manner and the knockout of Src impaired Ang II-mediated apoptosis and fibrosis in the cardiomyocytes. In addition, Src inhibition suppressed the expression of galectin-3 in vivo and in vitro. Specifically, AngII could upregulate the expression of galectin-3, and knockdown of galectin-3 (Gal-3) remarkably inhibited AngII-enhanced apoptosis and fibrosis in the cardiomyocytes. Furthermore, overexpression of galectin-3 reinforced Ang II-induced cell apoptosis and fibrosis that was attenuated by knockout of Src. Our findings indicate that Src and Gal-3 play an important role in AngII-mediated cardiac structural remodeling. Src and galectin-3 might serve as potential targets for the treatment of AngII-induced cardiac fibrosis and hypertrophy.