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-ß (TGF-ß) system, has been characterized in both animal models and in human lesions and lesion-derived cells. TGF-ß 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-ß activity in patients with atherosclerosis, and equally important changes in the way cells respond to TGF-ß during atherogenesis. Evidence from multiple sources indicates that experimental modulation of TGF-ß activity, or TGF-ß responses, changes the course of atherosclerosis and intimal hyperplasia. Cells derived from human lesions produce adequate TGF-ß levels, but are resistant to the antiproliferative and apoptotic effects of TGF-ß. An evolving theory describes TGF-ß 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.
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