Yixin Granules Reduce Myocardial Inflammation and Fibrosis in Rats with Heart Failure by Inhibiting the Expression of ADAMTS8.

Abstract

Yixin granules are medications modified from a Chinese prescription (Sheng Xian Tang) that has been used to alleviate shortness of breath. ADAM metallopeptidase with thrombospondin type 1 motif 8 (ADAMTS8) is upregulated in the myocardium of patients with dilated cardiomyopathy. Its high expression is associated with tumor necrosis factor (TNF) -α and myocardial fibrosis. This study aimed to explore the effect of Yixin granules on heart failure (HF) in rats and whether this effect is correlated with ADAMTS8 to provide new ideas for the treatment of HF.HF rat models were established by ligation of the left anterior descending coronary artery. Model rats were injected with adeno-associated virus vectors for the overexpression of ADAMTS8 and/or treated with Yixin granules for 4 weeks. Hematoxylin-eosin and Masson staining were used to detect myocardial injury and fibrosis, respectively. Reverse transcription polymerase chain reaction, western blotting, and/or enzyme-linked immunosorbent assay were used to detect the expression of ADAMTS8, TNF-α, interleukin (IL) -1β, IL-6, collagen I, collagen III, and α-smooth muscle actin in myocardium. The myocardial infarction area of rats was measured using 2,3,5-triphenyltetrazolium chloride staining.ADAMTS8 was upregulated in the myocardium of HF rats. Yixin granule treatment improved left ventricular contractility and reduced ADAMTS8 expression, myocardial injury, inflammation, and fibrosis in HF rats. ADAMTS8 overexpression aggravated myocardial injury, inflammation, and fibrosis. Moreover, ADAMTS8 overexpression counteracted the cardioprotective effects of Yixin granules.Yixin granules may reduce myocardial inflammation and fibrosis in HF rats by inhibiting the expression of ADAMTS8.