ADSC-derived exosomes attenuate myocardial infarction injury by promoting miR-205-mediated cardiac angiogenesis

Abstract

Abstract Background Acute myocardial infarction is a major health problem and is the leading cause of death worldwide. Myocardial apoptosis induced by myocardial infarction injury is involved in the pathophysiology of heart failure. Therapeutic stem cell therapy has the potential to be an effective and favorable treatment for ischemic heart disease. Exosomes derived from stem cells have been shown to effectively repair MI injury-induced cardiomyocyte damage. However, the cardioprotective benefits of adipose tissue-derived mesenchymal stem cell (ADSC)-Exos remain unknown. This study aimed to investigate the protective effects of exosomes from ADSC on the hearts of MI-treated mice and to explore the underlying mechanisms. Methods Cellular and molecular mechanisms were investigated using cultured ADSCs. On C57BL/6J mice, we performed myocardial MI or sham operations and assessed cardiac function, fibrosis, and angiogenesis 4 weeks later. Mice were intramyocardially injected with ADSC-Exos or vehicle-treated ADSCs after 25 min following the MI operation. Results Echocardiographic experiments showed that ADSC-Exos could significantly improve left ventricular ejection fraction, whereas ADSC-Exos administration could significantly alleviate MI-induced cardiac fibrosis. Additionally, ADSC-Exos treatment has been shown to reduce cardiomyocyte apoptosis while increasing angiogenesis. Molecular experiments found that exosomes extracted from ADSCs can promote the proliferation and migration of microvascular endothelial cells, facilitate angiogenesis, and inhibit cardiomyocytes apoptosis through miRNA-205. We then transferred isolated exosomes from ADSCs into MI-induced mice and observed decreased cardiac fibrosis, increased angiogenesis, and improved cardiac function. We also observed increased apoptosis and decreased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in HMEC-1 transfected with a miRNA-205 inhibitor. Conclusion In summary, these findings show that ADSC-Exos can alleviate cardiac injury and promote cardiac function recovery in MI-treated mice via the miRNA-205 signaling pathway. ADSC-Exos containing miRNA205 have a promising therapeutic potential in MI-induced cardiac injury.