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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1712.)
© 2006 American Heart Association, Inc.

Brief Reviews

Transforming Growth Factor-ßs and Vascular Disorders

Alex Bobik

From the Cell Biology Laboratory, Baker Heart Research Institute, Melbourne, Australia.

Correspondence to Professor Alexander Bobik, Cell Biology Laboratory, Baker Heart Research Institute, PO Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia. E-mail alex.bobik{at}baker.edu.au

Transforming growth factor-ß (TGF-ß) superfamily members, TGF-ß and bone morphogenetic proteins (BMPs), are potent regulatory cytokines with diverse functions on vascular cells. They signal through heteromeric type I and II receptor complexes activating Smad-dependent and Smad-independent signals, which regulate proliferation, differentiation, and survival. They are potent regulators of vascular development and vessel remodeling and play key roles in atherosclerosis and restenosis, regulating endothelial, smooth muscle cell, macrophage, T cell, and probably vascular calcifying cell responses. In atherosclerosis, TGF-ß regulates lesion phenotype by controlling T-cell responses and stimulating smooth muscle cells to produce collagen. It contributes to restenosis by augmenting neointimal cell proliferation and collagen accumulation. Defective TGF-ß signaling in endothelial cells attributable to mutations in endoglin or the type I receptor ALK-1 leads to hereditary hemorrhagic telangiectasia, whereas defective BMP signaling attributable to mutations in the BMP receptor II has been associated with development of primary pulmonary hypertension. The development of mouse models with either cell type–specific or general inactivation of TGF-ß/BMP signaling has started to reveal the importance of the regulatory network of TGF-ß/BMP pathways in vivo and their significance for atherosclerosis, hereditary hemorrhagic telangiectasia, and primary pulmonary hypertension. This review highlights recent findings that have advanced our understanding of the roles of TGF-ß superfamily members in regulating vascular cell responses and provides likely avenues for future research that may lead to novel pharmacological therapies for the treatment or prevention of vascular disorders.

TGF-ßs regulate diverse functions on vascular cells. They participate in atherosclerosis and restenosis regulating T-cell and smooth muscle cell functions. Defective signaling attributable to ALK-1 and endoglin mutations underlies development of hereditary hemorrhagic telangiectasia, whereas type II bone morphogenetic receptor mutations have been linked to primary pulmonary hypertension.

Key Words: TGF-ß • BMP • signaling • vascular cells • atherosclerosis • restenosis • hereditary hemorrhagic telangiectasia • pulmonary hypertension