title: Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects.
abstract: Age-related progression of cardiovascular disease is by far the largest health problem in the US and involves vascular damage, progressive vascular fibrosis and the accumulation of lipid-rich atherosclerotic lesions. Advanced lesions can restrict flow to key organs and can trigger occlusive thrombosis resulting in a stroke or myocardial infarction. Transforming growth factor-beta (TGF-β) is a major orchestrator of the fibroproliferative response to tissue damage. In the early stages of repair, TGF-β is released from platelets and activated from matrix reservoirs; it then stimulates the chemotaxis of repair cells, modulates immunity and inflammation and induces matrix production. At later stages, it negatively regulates fibrosis through its strong antiproliferative and apoptotic effects on fibrotic cells. In advanced lesions, TGF-β might be important in arterial calcification, commonly referred to as "hardening of the arteries". Because TGF-β can signal through multiple pathways, namely the SMADs, a MAPK pathway and the Rho/ROCK pathways, selective defects in TGF-β signaling can disrupt otherwise coordinated pathways of tissue regeneration. TGF-β is known to control cell proliferation, cell migration, matrix synthesis, wound contraction, calcification and the immune response, all being major components of the atherosclerotic process. However, many of the effects of TGF-β are essential to normal tissue repair and thus, TGF-β is often thought to be "atheroprotective". The present review attempts to parse systematically the known effects of TGF-β on both the major risk factors for atherosclerosis and to isolate the role of TGF-β in the many component pathways involved in atherogenesis.
authors.affiliation: Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 I Street NW. Ross Hall 443, Washington, DC 20037, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Toma
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McCaffrey
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012307:Risk Factors; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta