Turning Point in Myocarditis

Abstract

See related article, pages 462–470 Myocarditis is an acute inflammatory disease of the heart and a precursor of dilated cardiomyopathy.1–8 Myocarditis is often characterized by a cellular infiltrate, and if inflammation of the myocardium does not resolve during the acute stage, the heart may be compromised because of necrosis and direct loss of myocytes,9 injury from granulomatous inflammation,10,11 or fibrosis attributable to proliferation of fibroblasts and collagen deposition.12,13 Once the myocardium becomes fibrotic, there may be loss of function. In this issue of Circulation Research , Kania et al describe a novel system to study fibrosis in myocarditis and the origins of the fibrosis in a mouse model.14 Mice expressing enhanced green fluorescent protein (EGFP)+ were used as donors of prominin 1+ cells, which may directly lead to fibrosis during the development of the chronic disease state in myocarditis and cardiomyopathy. Prominin 1+ cells are precursors of fibroblasts in the bone marrow and, once injected into hearts, were shown to develop into fibroblasts and produce collagen in the presence of transforming growth factor (TGF)-β. Fibrosis could be blocked with anti–TGF-β treatment.14 These studies are directly applicable to human disease. TGF-β is a potential turning point, where therapy may prevent the chronic and destructive progression to irreversible end-stage dilated cardiomyopathy with lowered ejection fraction and loss of function in the heart. Dilated cardiomyopathy is a more chronic disease …