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Canadian Journal of Cardiology

ENDOTHELIAL COLONY-FORMING CELL-DERIVED EXTRACELLULAR VESICLES AND CARDIAC REPAIR AFTER MYOCARDIAL INFARCTION

      Background

      Despite improvements in therapeutics, ischemic heart disease remains a leading cause of death. Cardiac remodeling after myocardial infarction (MI), predominantly due to loss of cardiomyocytes and coronary vasculature, leads to a progressive decline in cardiac function resulting in heart failure. Current therapies for cardiac repair and heart failure are of limited benefit. Cell transplantation therapy upon MI is a very promising therapeutic strategy to replace dead myocardium, reducing scarring and improving cardiac performance.

      Methods and Results

      Our research focuses on endothelial colony-forming cell-derived exosomes (ECFC-exosomes), which are actively secreted endocytic nanovesicles (30-100 nm) that transport functional miRNAs, proteins, mRNAs, and lipids, playing a key role in paracrine intercellular communication. We identified a novel ability of ECFC-exosomes to promote angiogenesis and cardiac tissue repair. Administration of ECFCs to mice following experimental end-organ ischemia resulted in ECFC-exosome-dependent increase in angiogenesis. ECFC-derived exosomes were taken up by endothelial cells leading to their increased proliferation and migration, tube formation, and formation of new vessels. Administration of ECFC-exosome to a murine model of myocardial infarction prevented cardiac remodeling and heart failure. Next generation sequencing and bioinformatics analyses identified 136 miRNAs present in ECFC-exosome cargo, and factor inhibiting HIF-1α and PTEN as their potential targets in endothelial cells.

      Conclusion

      Our findings support the view that the ECFC-exosomes represent a novel therapeutic approach to improve cardiac repair and prevent the onset of heart failure after MI.