Chapter category: Extracellular Matrix
Myocardial Infarction and Cardiac Fibrosis
Chapter authors:
Shozo Kusachi and Yoshifumi Ninomiya
Fibrogenesis is essential for infarct healing and affects ventricular remodeling, one of the most important prognostic factors after myocardial infarction. Fibrogenesis is initiated by a variety of cytokines and growth factors produced by activated macrophages and inflammatory cells during the initial inflammatory phase. Fibroblasts that proliferate and infiltrate into the infarct zone are transformed into myofibroblasts, which express a variety of extracellular matrix (ECM) components that reconstruct the ECM in the infarcted myocardium. Following the inflammatory phase, fibrogenesis occurs prominently in the granulation tissue around the necrotic myocardium. Fibrillar collagens play major structural roles in infarct fibrosis. In addition to fibrillar collagens, basement membrane components of the ECM, type IV collagen, perlecan proteoglycan and laminin, appear in the infarct zone and also contribute to infarct ECM reconstruction. Other glycoproteins and proteoglycans are also expressed in the infarct zone and function in ECM reconstruction through their biological activity. Matricellular proteins modulate ECM reconstruction through paracrine and autocrine processes. Among various mediators of ECM homeostasis, transforming growth factor-b1 (TGF-b1), connective tissue growth factor (CTGF) and angiotensin II function importantly in promoting infarct fibrogenesis. Stretching of the myocardial wall and hypoxia are physiological factors that are specific to myocardial infarction and stimulate infarct fibrogenic processes through enhancing the levels of the fibrogenic mediators. Intercellular fibrosis also occurs in the noninfarct zone and TGF-b1 and angiotensin II promote this fibrosis. Reperfusion and pharmacological intervention may modulate infarct fibrogenic processes and limit ventricular remodeling.
