doi: 10.1161/01.RES.0000194559.35790.c5
© 2005 American Heart Association, Inc.
Editorials |
NO to Small Mothers Against Decapentaplegic (Smad)
From the Terrence Donnelly Research Laboratories, Division of Cardiology, St. Michael’s Hospital (P.F.H.L., D.W.C., D.J.S.), the Institute of Medical Science (P.F.H.L., D.J.S.), and the McLaughlin Centre for Molecular Medicine (D.J.S.), University of Toronto, Ontario, Canada.
Correspondence to Duncan J. Stewart, MD, FRCPC, FAHA, Professor of Medicine and Dexter H.C. Man Chair of Cardiology, University of Toronto, Room 6-050k, Queen Wing, Terrence Donnelly Heart Centre, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada. M5B 1W8. E-mail stewartd@smh.toronto.on.ca
See related article, pages 1115–1123
Key Words: nitric oxide • transforming growth factor-ß • Smads • signal transduction
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Transforming Growth Factor-ß (TGF-ß) is the prototype of a superfamily of multifunctional proteins which includes activins and bone morphogenetic proteins (BMPs). TGF-ß is involved in the regulation of diverse cellular processes such as cell proliferation, differentiation, apoptosis and migration, as well as moderating cell–cell and cell–matrix interactions. It plays a pivotal role in embryonic development, and perturbations of TGF-ß signaling may have profound pathological consequences in a wide variety of diseases. (For general reviews on TGF-ß actions, please see Massagué1 and Kim et al.2)
Cellular responses to TGF-ß are complex and, depending on cell type and conditions, it can induce stimulatory or inhibitory effects. In the heart, TGF-ß stimulates hypertrophy of cardiomyocytes and proliferation of fibroblasts, contributing to myocardial fibrosis and dysfunction.3 In the blood vessel wall, TGF-ß inhibits proliferation and migration of vascular smooth muscle cells, and defective signaling can lead to pathological vascular remodeling.4 TGF-ß is also a potent suppressor of leukocyte activation, and under some conditions can exert a protective immunomodulatory role in atherosclerosis.5,6 TGF-ß can act as an inhibitor or a stimulator of endothelial proliferation, impacting on different stages of angiogenesis.7,8 Despite the diversity in actions, a recurring theme for TGF-ß in the cardiovascular system is the stimulation of increased matrix production and tissue remodeling. Amplification of the TGF-ß response is also commonly observed, attributable to autoinduction of the TGF-ß gene.9
Because TGF-ß is involved in such a vast diversity of regulation of cellular events, it is therefore not surprising that its signaling is characterized
Related Article:
Circ. Res. 2005 97: 1115-1123.