Yin and Yang of Myocardial Transforming Growth Factor-β 1

Abstract

Ischemic heart disease is a leading cause of chronic myocardial failure and mortality in the United States.1 After myocardial infarction (MI), the heart undergoes a well-characterized process of deleterious structural and molecular remodeling, marked by ventricular dilation, infarct wall thinning, and replacement fibrosis, with a corresponding progressive impairment of contractile function.2 Recent work has suggested that supplementation of myocardial cells with exogenous bone marrow–derived stem cell populations may have the potential to regenerate lost cardiomyocytes and slow, or even reverse, the remodeling process.3 Although the importance of both postinjury myocardial remodeling and regeneration are well accepted, the critical mechanisms that underlie these processes remain unclear. As insight into the biology of myocardial injury and dysfunction increases, the role of stress-activated cytokines has achieved particular prominence.4 Two articles in this issue of Circulation highlight the importance of the stress-activated cytokine, transforming growth factor (TGF)-β1, in mediating the complex processes of cardiac remodeling and regeneration. See pp 2430 and 2438 First isolated >20 years ago, TGF-β was identified from sarcoma cells based on its ability to potentiate the transforming and proliferative actions of epidermal growth factor on non-neoplastic fibroblasts.5,6 Since then, the TGF-β family has grown rapidly and at present consists of >30 structurally related members, including TGF-β1. This diverse cytokine superfamily has been subgrouped according to sequence similarity and specific downstream signaling pathways into the TGF-β/activin/nodal family and the bone morphogenic protein/growth and differentiation factor/Muellerian inhibiting …