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Submitted on July 29, 2002
Accepted on September 30, 2002
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.
* To whom correspondence should be addressed. E-mail: mrb{at}mole.bio.cam.ac.uk.
ObjectiveWe sought to identify differentially expressed genes in human in stent stenosis (ISS) to provide insights into the mechanism of disease.
Methods and ResultsUsing 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.
ConclusionsISS 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.
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