© 2001 American Heart Association, Inc.
Editorials |
Transforming Growth Factor-ß
A Local or Systemic Mediator of Plaque Stability?
From the Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands.
Correspondence to Mat J.A.P. Daemen, Dept of Pathology, P. Debeyelaan 25, 6202 AZ Maastricht, Netherlands. E-mail mda@lpat.azm.nl
See related article, pages 930–934
Key Words: atherosclerosis • inflammation • fibrosis • transforming growth factor-ß • unstable plaque
Atherosclerosis is mainly considered to be a chronic inflammatory disease.1,2 The importance of inflammatory mediators in the initiation and progression of atherosclerosis is reflected by the composition of the atherosclerotic lesion and by many intervention studies in mouse models of atherosclerosis. Activated macrophages and T-lymphocytes are already observed in fatty streak lesions,3 and the contribution of inflammatory cells and mediators increases when the atherosclerotic lesion progresses.4 Furthermore, intervention studies in atherosclerotic mouse models that inhibit major (anti)inflammatory mediators such as CD40L,5–9 gm-CSF,10,11 MCP1,12 IFN
,13 and IL-1014,15 have a profound effect on lesion initiation, progression, and plaque composition.
So far, IL-10 is the only antiinflammatory cytokine that has been reported to be protective in atherosclerosis.15,16 In the present issue of Circulation Research, the study by Mallat et al17 showed that inhibition of the antiinflammatory cytokine transforming growth factor (TGF)-ß resulted in an acceleration of atherosclerosis. Moreover, atherosclerotic lesions exhibited an increased inflammatory cell content and a decrease in collagen content, which are features of plaque instability. The data of Mallat et al indicate that TGF-ß plays a protective role in the initiation of atherosclerosis and may be an important factor for the maintenance of plaque stability.
The feature that inhibition of inflammatory mediators or stimulation of antiinflammatory mediators modulate atherosclerotic plaque stability has already been shown in several studies. For example, interventions in atherosclerotic mouse models with major inflammatory regulators such as CD40L,5,6,8,9 IFN,13 and IL1014 are able to modulate features of plaque stability, such as the amount
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