Investigate the Pathophysiological Roles and Therapeutic Potentials of Exosome in High-Fat Diet-Induced Cardiac Hypertrophy.

There is a growing body of evidence indicates that cardiac hypertrophy is the precursor lesion and independent risk factors of coronary heart disease, heart failure, and sudden cardiac death. However, the underlying pathogenesis and distinct mechanisms of cardiac hypertrophy are not fully understood, thus limiting the development of novel preventive and treatment strategies. A study from 13 advanced congestive heart failure patients found that immunoadsorption was able to improve endothelial function by reducing the circulating and endothelial-derived extracellular vesicle (EV), indicating that EV are probably involved in the pathological processes of cardiomyopathy and may also have a potential in reflecting the outcome or prognostics of cardiomyopathy. Exosome (EXO) is nano-range EV, which are actively secreted out by different type of cells and are present in almost all body fluids. It has been demonstrated that exosomal micro RNAs (miRNAs) are involved in the pathogenesis of heart diseases. However, the role of exosomes in cardiac hypertrophy has not been elucidated completely yet, and requires further investigations to clarify it. Our laboratory has established high-fat diet (HFD)-induced cardiac hypertrophic mice model for studying the pathogenesis of insulin resistant or diabetic cardiomyopathy. In addition, EXO purification and characterization techniques have been building up in our lab. Therefore, in this three years project, we plan to discover the pathological biomarkers from HFD-EXO in 1st year and will investigate the pathophysiological roles of EXO in angiotensin II-induced H9C2 cardiomyocyte hypertrophy (in vitro) and in HFD-induced cardiac hypertrophy mice (in vivo) in 2nd year. In the 3rd year, the therapeutic potentials of synthetic EXO (siRNA and miRNA loaded artificial EXO, RNArt-EXO) will be evaluated in both in vitro and in vivo systems. Significance: The anticipated results will provide a safe and convenient method for early diagnosis and our novel EXO-based drug, synthetic RNArt-EXO, can provide as a potential therapeutic strategy for heart diseases.

Project ID:PC10907-1533
External Project ID:MOST109-2320-B182-005