Getting to the heart of myofibroblast differentiation: implications for scleraxis in ECM remodeling and therapeutic targeting

Myofibroblasts are major contributors to cardiac remodeling after injury. The extracellular matrix (ECM) is a dynamic, acellular scaffold of structural proteins (such as collagen, fibronectin, integrins, and cadherins) maintained by fibrocytes (quiescent, immotile, low ECM-modifying) and fibroblasts (proliferative, motile, high ECM-modifying) within the interstitial space. The essential ECM regulates cell migration, cardiomyocyte alignment, and maintains proper chamber morphology and mechanical function. As cardiomyocytes possess little regenerative capacity in the adult heart, increased ECM deposition in the form of a fibrotic scar is essential to maintain ventricular wall integrity and function after myocardial infarction.