Transforming Growth Factor-β

Abstract

Cardiac remodeling is a term that broadly refers to changes in myocardial structure and function in response to injury. Irrespective of the injurious mechanism (ie, myocardial infarction, hypertensive heart disease, valvulopathy, myocarditis, or primary myocyte dysfunction), a decline in ventricular function activates several compensatory pathways designed to sustain tissue perfusion. Among these cascades, the sympathetic nervous system, the renin-angiotensin-aldosterone system, and the transforming growth factor-β (TGF-β) system stimulate myocyte hypertrophy and cardiac fibrosis. Traditionally, this paradigm of cardiac remodeling is applied to subjects with heart failure and reduced left ventricular ejection fraction; however, the precise molecular mechanisms underlying the pathophysiology of heart failure with preserved ejection fraction (HFpEF) are poorly understood. Article see p 44 Although much attention has focused on myocyte biology in heart failure, regulation of cardiac fibrosis in the context of HFpEF remains an area of active investigation. The cardiac fibroblast is the primary cell type responsible for generating extracellular matrix (ECM) within the myocardium. This ECM is composed primarily of type I collagen (80%) and type III collagen (10%). The remaining 10% is composed of type V and type VI collagen, laminin, elastin, glycosaminoglycans, and proteoglycans.1 This collagen network provides mechanical support to the myocardium, organizes muscle contraction, synthesizes and releases growth factors in a paracrine and autocrine fashion, and promotes wound healing. The term fibrosis encompasses several processes including fibroblast proliferation, collagen synthesis and degradation, and conversion of fibroblasts …