Mechanoregulation of Myofibroblast Fate and Cardiac Fibrosis

During myocardial infarction, myocytes die and are replaced by a specialized fibrotic extracellular matrix, otherwise known as scarring. Fibrotic scarring presents a tremendous hemodynamic burden on the heart, as it creates a stiff substrate, which resists diastolic filling. Fibrotic mechanisms result in permanent scarring which often leads to hypertrophy, arrhythmias, and a rapid progression to failure. Despite the deep understanding of fibrosis in other tissues, acquired through previous investigations, the mechanisms of cardiac fibrosis remain unclear. Recent studies suggest that biochemical cues as well as mechanical cues regulate cells in myocardium. However, the steps in myofibroblast transdifferentiation, as well as the molecular mechanisms of such transdifferentiation in vivo, are poorly understood. This review is focused on defining myofibroblast physiology, scar mechanics, and examining current findings of myofibroblast regulation by mechanical stress, stiffness, and topography for understanding fibrotic disease dynamics.