Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

• Published in: Cellular physiology and biochemistry Vol. 44; no. 6; pp. 2105 - 2116
• Main Authors: Luo, Qiancheng, Guo, Dongfeng, Liu, Guorong, Chen, Guo, Hang, Min, Jin, Mingming
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Acute myocardial ischaemia; Adipose Tissue - cytology; ADSCs; Angiogenesis; Animals; Apoptosis; Cell Line; Cells, Cultured; Exosomes; Exosomes - genetics; Gene expression; Gene Expression Regulation; Genetic Therapy; Heart attacks; Immunoglobulins; Inflammation; Kinases; Laboratory animals; Male; MicroRNAs; MicroRNAs - genetics; MiR-126; Myocardial Infarction - genetics; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neovascularization, Physiologic; Original Paper; Rats; Rats, Sprague-Dawley; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transplants & implants; Up-Regulation; United States > US; China; MiR-126; ADSCs; Exosomes; Acute myocardial ischaemia; Apoptosis
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000485949

Background/Aims: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). Methods: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. Results: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. Conclusions: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis.