Gene Therapy for Cardiomyocyte Renewal: Cell Cycle, a Potential Therapeutic Target.

Heart disease is the primary cause of death worldwide. Even though extensive research has been done, and many pharmacological and surgical treatments have been introduced to treat heart disease, the mortality rate still remains high. Gene therapy is widely used to understand molecular mechanisms of myocardial infarction and to treat cardiomyocyte loss. It was reported that adult cardiomyocytes proliferate at a very low rate; thus, targeting their proliferation has become a new regenerative therapeutic approach. Currently, re-activating cardiomyocyte proliferation appears to be one of the most promising methods to promote adult cardiomyocyte renewal. In this article, we highlight gene therapeutic targets of cell proliferation presently being pursued to re-activate the cell cycle of cardiomyocytes, including cell cycle regulators, transcription factors, microRNAs, signal transduction, and other contributing factors. We also summarize gene delivery vectors that have been used in cardiac research and major challenges to be overcome in the translation to the clinical approach and future directions.