Proregenerative MicroRNAs to Repair the Damaged Heart

Cardiac regeneration remains a major challenge in clinical medicine. Following MI, up to 25% of cardiomyocytes in the left ventricle can be lost, a key factor contributing to heart failure. In adults, this loss is not compensated by new cardiomyocyte formation. However, in neonatal mammals and some other species, such as fish and amphibians, heart regeneration occurs naturally through the proliferation of the surviving cardiomyocytes. Over the past two decades, substantial progress has been made in understanding the molecular pathways that regulate cardiomyocyte proliferation during development, early neonatal life and in other species. Notably, several human microRNAs, identified through extensive screening for their ability to stimulate cell proliferation, have emerged as potent inducers of cardiomyocyte proliferation and cardiac regeneration when administered therapeutically. This review highlights the gene targets and regenerative effects of the most effective of these microRNAs, including the miR-17-92 and miR-302-367 clusters, miR-199a, miR-1825, miR-590 and miR-33b, and discusses their potential for clinical application in treating MI and heart failure.