Myofibroblasts and smooth muscle cells in human myocardial scars: Possible origins and inductive factors

Necrotic myocardial lesions, including myocardial infarcts, heal by formation of scar tissue, and it is commonly thought that fibroblasts are the principal cells producing and maintaining the scar tissue matrix. In contrast to this notion, our study of old myocardial scars in 11 human hearts revealed that myofibroblasts (MFBs) and nonvascular smooth muscle cells (SMCs) were the dominant cell types. Both contractile cell types stained positively with antibody to α-smooth muscle actin and were identified ultrastructurally by the presence of nonsarcomeric myofibrillar elements. They were distinguished from each other by basal lamina, which invested the SMCs but not the MFBs. Neither cell type was identified in the myocardium of 3 normal human hearts, where fibroblasts were the normal interstitial cells. In earlier studies, we made similar observations in rat heart scars. The presence of MFBs and SMCs in myocardial scar tissue but not in normal myocardium raises questions about their origins, lineage relationships, inductive mechanisms, and functions. The results of our studies indicated that the MFB and SMC phenotypes were induced and maintained by the cyclical physical forces associated with myocardial contractions; that fibroblasts and MFBs seemed to be phenotypic modulations of the same cell type in a physical environment favoring expression of the MFB form; that the nonvascular SMCs were not derived from MFBs but may have come from cells located in vessel walls; and that the contractile cells in scar tissue might resist and counteract the stretching forces induced by myocardial contractions.