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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:2030.)
© 2002 American Heart Association, Inc.

Atherosclerosis

Differential Gene Expression in Vascular Smooth Muscle Cells in Primary Atherosclerosis and In Stent Stenosis in Humans

Qi Jun Zhang; Martin Goddard; Catherine Shanahan; Leonard Shapiro; Martin Bennett

From the Division of Cardiovascular Medicine (Q.J.Z., C.S., M.B.), Addenbrooke’s Centre for Clinical Investigation, Addenbrooke’s Hospital and Department of Histopathology (M.G.) and Cardiac Unit (L.S.), Papworth Hospital, Cambridge, UK.

Correspondence to Professor Martin R Bennett, Division of Cardiovascular Medicine, Box 110, Addenbrooke’s Centre for Clinical Investigation, Addenbrooke’s Hospital, CB2 2QQ, Cambridge, UK. E-mail mrb{at}mole.bio.cam.ac.uk

Abstract

Objective— We sought to identify differentially expressed genes in human in stent stenosis (ISS) to provide insights into the mechanism of disease.

Methods and Results— Using representation difference analysis, we examined differential gene expression between cultured normal human medial vascular smooth muscle cells (VSMCs) and cells from primary atherosclerotic plaques or ISS sites. Specific groups of genes were overexpressed in ISS and plaque VSMCs, including cell cycle regulatory proteins and cell matrix and contractile proteins. Differential expression was validated by virtual Northern analysis, reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunohistochemistry. All ISS genes were expressed by normal intima and had even higher expression in primary plaque VSMCs.

Conclusions— ISS VSMCs have a stable gene expression profile reflecting an intimal pattern, intermediate between normal medial and primary plaque VSMCs. Differential expression profiling may identify markers of disease that are overexpressed in ISS and also help elucidate the origin of the ISS lesion.

Key Words: arteriosclerosis • restenosis • stents • genes • smooth muscle

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