Transforming Growth Factor β and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 3; pp. 399 - 404
• Main Author: Grainger, David J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.03.2004; Hagerstown, MD Lippincott
• Subjects: Animals; Arteriosclerosis - etiology; Arteriosclerosis - metabolism; Arteriosclerosis - prevention & control; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Extracellular Matrix - metabolism; Humans; Inflammation; Medical sciences; Mice; Mice, Knockout; Models, Biological; Muscle, Smooth, Vascular - physiology; Signal Transduction; Species Specificity; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transforming Growth Factor beta - deficiency; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; Tunica Intima - physiology; Vascular disease; Myocardial infarction; Prevention; Transforming growth factor β; Heart disease; Atherosclerosis; Cytokine; Cardiovascular disease; TGF-β; Inflammation; Myocardial disease
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/01.ATV.0000114567.76772.33

ABSTRACT—The role of the anti-inflammatory cytokine transforming growth factor β (TGF-β) in atherosclerosis has been the subject of considerable debate for a decade. In the early 1990s, we postulated that TGF-β played an important role in maintaining normal vessel wall structure and that loss of this protective effect contributed to the development of atherosclerosis. We termed this the protective cytokine hypothesis. This proposal was slow to gain broad acceptance, however, because at that time there were little data available on the role of TGF-β during the development of atherosclerosis but much information about its role during trauma-induced neointima formation. Because TGF-β apparently aggravates neointima formation, both by inhibiting endothelial regeneration and by promoting fibrosis, it was difficult to accept that its presence might ameliorate the superficially similar atherogenesis process. But several recent studies revealed beyond doubt the fact that TGF-β protects against lipid lesion formation, at least in mouse models of atherosclerosis. Therefore, two important questions remain. First, is the role of TGF-β in vascular biology similar in humans and in mice? Secondly, how important, compared with defects in thrombosis or lipoprotein metabolism, is the protective role of TGF-β during atherogenesis?