Notch Signaling as an Important Mediator of Cardiac Repair and Regeneration After Myocardial Infarction

Through local cell-cell interactions, the Notch signaling pathway controls tissue formation and homeostasis during embryonic and adult life. In the heart, Notch1 is expressed in a variety of cell types, such as cardiomyocytes, smooth muscle cells, and endothelial cells. In cardiomyocytes, Notch1 is activated in proliferating embryonic and immature cardiomyocytes, and it is downregulated in the myocardium during postnatal development. However, Notch signaling in the adult myocardium could be activated transiently in response to myocardial injury, suggesting that Notch signaling may contribute to cardiac repair. Indeed, activation of Notch1 intracellular domain blunts the severity of myocardial injury and improves myocardial hemodynamic function. Conversely, genetic ablation of the Notch1 gene, either systemically or in bone marrow-derived cells, leads to impaired cardiac repair following myocardial infarction. In this review, we discuss the complex mechanisms of Notch signaling and its role in cardiac repair and regeneration after myocardial infarction.