Bone marrow mesenchymal stem cell-derived exosomes attenuate cardiac hypertrophy and fibrosis in pressure overload induced remodeling.

Abstract

The multiple therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) have been verified in ischemic and reperfusion diseases. Exosomes are thought to play vital roles in MSCs-related cardioprotective effects. Recently, more and more evidences indicated that apoptosis and fibrosis were crucial pathological mechanisms in cardiac remodeling. Whether MSCs-derived exosomes could regulate cardiac hypertrophy and remodeling need to be explored. Murine BM-MSCs-derived exosomes were isolated by differential gradient centrifugation method. The transverse aortic constriction (TAC) mice model was established to promote cardiac remodeling. Cardiac function and remodeling were assessed via echocardiography and histology analysis. Myocytes apoptosis was determined by TUNEL fluorescence staining. Meanwhile, premature senescence was detected by β-galactosidase (SA-β-gal) staining. Related proteins and mRNA alternation were assessed via western blotting and quantitative reverse transcription polymerase chain reaction, respectively. MSCs-derived exosomes significantly protected myocardium against cardiac hypertrophy, attenuated myocardial apoptosis, and fibrosis and preserved heart function when pressure overload. In cultured myocytes, MSCs-derived exosomes also prevented cell hypertrophy stimulated with angiotensin II. One the other hand, exosomes promoted premature senescence of myofibroblasts vitro, indicating its anti-fibrosis effect in cardiac remodeling. Exosomes protected cardiomyocytes against pathological hypertrophy. It may provide a promising future treatment for heart failure.