Epigallocatechingallate attenuates myocardial injury in a mouse model of heart failure through TGF­ß1/Smad3 signaling pathway.

ABSTRACT

The present study aimed to assess the protective effect of epigallocatechingallate (EGCG) against myocardial injury in a mouse model of heart failure and to determine the mechanism underlying regulation of the transforming growth factor­ß1/mothers against decapentaplegic homolog 3 (TGF­ß1/Smad3) signaling pathway. Mouse models of heart failure were established. Alterations in ejection fraction, left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs) were measured by echocardiography. Pathological alterations of myocardial tissue were determined by hematoxylin and eosin, and Masson staining. The levels of serum brain natriuretic peptide (BNP), N­terminal­proBNP, interleukin (IL)­1ß, IL­6, tumor necrosis factor­α, malondialdehyde, superoxide dismutase and glutathione peroxidase were detected with ELISA. Expression of collagen I, collagen III were detected by western blotting and reverse transcription quantitative polymerase chain reaction. Transforming growth factor­ß1 (TGF­ß1), Smad3, phosphorylated (p)­Smad3, apoptosis regulator BAX (Bax), caspase­3 and apoptosis regulator Bcl2 in mouse cardiac tissue were measured by western blotting. P­smad3 and TGF­ß1 were measured by immunofluorescence staining. EGCG reversed the alterations in LVIDd and LVIDs induced by establishment of the model of heart failure, increased ejection fraction, inhibited myocardial fibrosis, attenuated the oxidative stress, inflammatory and cardiomyocyte apoptosis and lowered the expression levels of collagen I and collagen III. Following treatment with TGF­ß1 inhibitor, the protective effect of EGCG against heart failure was attenuated. The results of the present study demonstrated that EGCG can inhibit the progression and development of heart failure in mice through inhibition of myocardial fibrosis and reduction of ventricular collagen remodeling. This protective effect of EGCG is likely mediated through inhibition of TGF­ß1/smad3 signaling pathway.