Human Hearts Intrinsically Increase Cardiomyocyte Mitosis After Myocardial Infarction.

Abstract

Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes within the human heart. Although cardiomyocytes undergo mitosis during early development, most cardiomyocytes cease cell cycling soon after birth. In contrast, rodent MI models have shown that cardiomyocytes increase mitosis in response to ischemia; however, this has not been shown in humans. Using a unique premortem post-MI human heart, immunostaining, bulk RNA sequencing, proteomics, metabolomics, single-nucleus RNA sequencing and a novel post-MI human biopsy method, we investigated human cardiomyocyte mitosis post-MI. We show that adult human cardiomyocytes exhibit increased mitosis and cytokinesis in response to ischemia. Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration.