PR002737 (Project)

Description:Background: Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes (CMs) within the human heart. Although CMs undergo mitosis during early development, most CMs cease cell cycling soon after birth. In contrast, rodent MI models have shown that CMs increase mitosis in response to ischemia, however this has not been shown in humans. Methods: Using a unique pre-mortem 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 CM mitosis post-MI. Results: We show that adult human CMs exhibit increased mitosis and cytokinesis in response to ischemia. Conclusions: Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration.