The cardiomyocyte cell cycle in hypertrophy, tissue homeostasis, and regeneration.

Mammalian cardiomyocytes withdraw from the cell cycle shortly after birth. Although the adult heart is unable to regenerate, numerous reports have shown that adult cardiomyocytes exhibit a dynamic range of cell cycle activity under various physiological and pathological conditions. Reason and consequence of cardiomyocyte cell cycle activity remain unclear and have led to a number of misconceptions. Understanding the scenarios in which cycling happens may promote new perspectives on the differentiated state of cardiomyocytes, treatments for hypertrophy, heart regeneration and cancer therapy. In this review we discuss the result of cardiomyocyte cell cycle activity in aging and disease and studies manipulating cardiac cell cycle activity to promote cardiac regeneration. In addition, we focus on cardiomyocyte differentiation, cell cycle exit, and the relationship between ploidy and regenerative potential. Finally, we provide observations that may further advance the goal of inducing adult mammalian heart regeneration through cardiomyocyte proliferation.