Adult mammalian cardiomyocytes (CMs) exhibit limited proliferative capacity, as cell cycle
activity leads to an increase in DNA content, but mitosis and cytokinesis are infrequent. This
makes the heart highly inefficient in replacing with neoformed cardiomyocytes lost contractile cells as
occurs in diseases such as myocardial infarction and dilated cardiomyopathy. Regenerative therapies
based on the implant of stem cells of diverse origin do not warrant engraftment and electromechanical
connection of the new cells with the resident ones, a fundamental condition to restore the physiology
of the cardiac syncytium. Consequently, there is a growing interest in identifying factors playing relevant
roles in the regulation of the CM cell cycle to be targeted in order to induce the resident cardiomyocytes
to divide into daughter cells and thus achieve myocardial regeneration with preservation of
physiologic syncytial performance.
Despite the scientific progress achieved over the last decades, many questions remain unanswered, including
how cardiomyocyte proliferation is regulated during heart development in gestation and neonatal
life. This can reveal unknown cell cycle regulation mechanisms and molecules that may be manipulated
to achieve cardiac self-regeneration.
We hereby revise updated data on CM cell cycle regulation, participating molecules and pathways recently
linked with the cell cycle, as well as experimental therapies involving them.