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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:555.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Microsatellite Mutation of Type II Transforming Growth Factor-ß Receptor Is Rare in Atherosclerotic Plaques

Katherine J. Clark; Nathaniel R. Cary; Andrew A. Grace; James C. Metcalfe

From the Section of Cardiovascular Biology, Department of Biochemistry (A.A.G., J.C.M.) and the Department of Oncology, MRC Centre (K.J.C.), University of Cambridge, Cambridge, UK, and the Directorate of Forensic Pathology, Department of Forensic Medicine (N.R.C.), Guy’s, King’s, and St. Thomas’s Hospital Medical School, London, UK.

Correspondence to Katherine J. Clark, PhD, Department of Oncology, University of Cambridge, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK. E-mail kc216{at}mole.bio.cam.ac.uk

Abstract—A somatic mutation within a microsatellite polyA tract in the coding region of the type II transforming growth factor (TGF)-ß receptor gene was reported to occur in human atherosclerotic and restenotic lesions. This mutation occurs frequently in colorectal cancer with the replication error repair phenotype and results in loss of sensitivity to the growth inhibitory effects of TGF-ß in cells from the tumors. The mutation was proposed to account for the clonal expansion of vascular smooth muscle cells observed in atherosclerotic plaques, through loss of the growth inhibitory effect of TGF-ß. The frequency of the mutation and the extent of clonal expansion of the mutated cells have major implications for the mechanism of atherogenesis and therapeutic strategies. We analyzed a set of 22 coronary arterial and 9 aortic samples containing early to advanced atherosclerotic lesions for the mutation in the type II TGF-ß receptor polyA tract. Only 1 coronary arterial sample from an advanced lesion showed detectable amounts of the mutation, present at a low level (8% of the DNA sample). The data imply that the mutation occurs only at low frequency and is not a major mechanistic contributor to the development of atherosclerosis.

Key Words: transforming growth factor-ß • type II transforming growth factor-ß receptors • microsatellite mutation • atherosclerosis

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