title: TGF-beta signaling in atherosclerosis and restenosis.
abstract: Current theories suggest that atherosclerotic and restenotic lesions result from imbalances between systems that are proinflammatory/fibroproliferative versus the endogenous inhibitory systems that normally limit inflammation and vascular wound repair. Abnormalities in one of the major regulatory pathways, the transforming growth factor-beta (TGF-beta) system, has been characterized in both animal models and in human lesions and lesion-derived cells. TGF-beta signaling is capable of regulating many of the key aspects of atherosclerosis and restenosis: inflammation, chemotaxis, fibrosis, proliferation, and apoptosis. There are significant decreases in TGF-beta activity in patients with atherosclerosis, and equally important changes in the way cells respond to TGF-beta during atherogenesis. Evidence from multiple sources indicates that experimental modulation of TGF-beta activity, or TGF-beta responses, changes the course of atherosclerosis and intimal hyperplasia. Cells derived from human lesions produce adequate TGF-beta levels, but are resistant to the antiproliferative and apoptotic effects of TGF-beta. An evolving theory describes TGF-beta as a major orchestrator of the vascular repair process, with observable defects in its production, activation, and cellular responses during the atherosclerotic and restenotic processes.
authors.affiliation: The George Washington University Medical Center, Department of Biochemistry and Molecular Biology, The Catharine Birch McCormick Genomics Center, and The Richard B. and Lynne V. Cheney Cardiovascular Institute, Washington, D.C. USA. mcc@gwu.edu
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McCaffrey
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D023903:Coronary Restenosis / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta