Mechanisms of cardiac fibrosis in inflammatory heart disease

Abstract

Heart injury from many causes can end up in a common final pathway of pathologic remodeling and fibrosis, promoting heart failure development. Dilated cardiomyopathy is an important cause of heart failure and often results from virus-triggered myocarditis. Monocytes and monocyte-like cells represent a major subset of heart-infiltrating cells at the injury site. These bone marrow-derived cells promote not only tissue injury in the short term but also angiogenesis and collagen deposition in the long term. Thus, they are critically involved in the typical tissue fibrosis, which evolves in the dilating ventricle during the process of pathologic remodeling. Recent findings suggest that heart-infiltrating monocyte-like cells indeed contain a pool of progenitors, which represent the cellular source both for accumulation of differentiated monocytes during the acute inflammatory phase and for transforming growth factor-beta-mediated myocardial fibrosis during the later chronic stages of disease. Obviously, a delicate balance of proinflammatory and profibrotic cytokines dictates the fate of bone marrow-derived heart-infiltrating progenitors and directly influences the morphologic phenotype of the affected heart. In this minireview, we provide an update on these mechanisms and discuss their significance in pathologic remodeling and heart failure progression after myocarditis.