on December 29, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print December 29, 2003, doi: 10.1161/01.ATV.0000114567.76772.33
Published online before print December 29, 2003, doi: 10.1161/01.ATV.0000114567.76772.33
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Submitted on July 9, 2003
Accepted on July 30, 2003
Transforming Growth Factor 
and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis
David J. Grainger *
From the Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
* To whom correspondence should be addressed. E-mail: djg15{at}cam.ac.uk.
Abstract--The role of the anti-inflammatory cytokine transforming growth factor 
(TGF-) in atherosclerosis has been the subject of considerable debate for a decade. In the early 1990s, we postulated that TGF- 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- during the development of atherosclerosis but much information about its role during trauma-induced neointima formation. Because TGF- 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- protects against lipid lesion formation, at least in mouse models of atherosclerosis. Therefore, two important questions remain. First, is the role of TGF- 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- during atherogenesis?
Key words: TGF-
•
myocardial infarction •
inflammation
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