To Investigate the Protective Role of Cardiac Fibroblast-Derived Exosomal Mir-30a in a Rat Acute Myocardial Infarction Model

In response to stress, the heart undergoes cardiac remodeling that results in cardiac hypertrophy and cardiac fibrosis, which contribute to heart failure. Conditioned medium derived from the ischemic ventricular myocardium improves the cardiac function of rats after myocardium infraction. Exosomal microRNA-mediated cell-to-cell communication is suggested to mediate the protective effect of conditioned medium against ischemic or oxidative injuries. The major object of this proposal is to investigate the role of exosomal microRNA, miR-30a, from cardiac fibroblasts during cardiac remodeling after acute myocardial infarction.Cardiomyocytes and cardiac fibroblasts are two dominating cell types in the process of cardiac remodeling. In the ischemic condition, both cardiac fibroblasts and cardiomyocytes will be activated to face the environmental stresses. Upon stress or various cardiac diseases, microRNAs have been found to be involved in modulating the pathological processes. Growing evidence shows that the exosomal microRNAs could be key players in intercellular cross-talk, particularly during different diseases, such as myocardial infraction and heart failure. Recent studies have shown that exosomal microRNAs from endothelial cells has the ability in regulating proliferation and gene expression in arterial smooth muscle cells. Our recent study has demonstrated that exosomal microRNAs released from cardiomyocytes play a role in mediating the protective effects of conditioned medium on ameliorating myocardial injury. Although the expression levels of microRNAs have been found to be involved in cardiac hypertrophy and acute myocardial infarction, the roles in exosomal microRNAs communication between cardiac cells are still unknown. Therefore, in this proposal, we will apply in vitro cultured cells model to examine the expression profiles of intra-cellular and exosomal microRNA, miR-30a, of cardiac fibroblasts. We will also use the over-expression and knockdown strategies to examine the role of exosomal miR-30a in cellular responses after ischemic and oxidative stresses. Finally, the in vivo animal models with acute myocardial infarction will apply to determine the role of exosomal miR-30a in conditioned medium-mediated cardiac function preservation after AMI.

Project ID:PC10908-0260
External Project ID:MOST109-2635-B182-001