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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1283.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Atherosclerotic Plaque Smooth Muscle Cells Have a Distinct Phenotype

Eileen R. Mulvihill; Jochen Jaeger; Rimli Sengupta; Walter L. Ruzzo; Cecile Reimer; Sheila Lukito; Stephen M. Schwartz

From the Departments of Pathology (E.R.M., C.R., S.M.S.) and Computer Science and Engineering (J.J., R.S., W.L.R.) and the School of Pharmacy (S.L.), University of Washington, Seattle, Wash; the Max Planck Institute for Molecular Genetics (J.J.), 14195 Berlin, Germany; and the Department of Computer Science and Engineering (R.S.), IIT, Kharagpur, India.

Correspondence to Dr Eileen R. Mulvihill, University of Washington, Department of Pathology, Box 357335, Seattle, WA 98195-7335. E-mail mulvie{at}u.washington.edu

Objective— The present study addresses the question, "Are plaque smooth muscles cells (SMCs) genetically distinct from medial SMCs as reflected by the ability to maintain a distinctive expression phenotype in vitro?"

Methods and Results— Multiple cell strains were developed from carotid endarcterectomy specimens, and quadruplicate array hybridizations were completed for each sample. A new normalization protocol was developed and used to analyze the data. Permutation analysis suggests that most of the significant differences in expression could not have occurred by chance. A broad pattern of significant expression differences, consisting of almost 5% of the genes probed, was detected. Quantitative polymerase chain reaction (QPCR) confirmation was found in 70% of a subset of genes selected for validation.

Conclusions— The SMC cultures were nearly indistinguishable by morphological features, population doubling time, and sensitivity to cell death induced by Fas cross-linking. Surprisingly, array expression analysis identified differences so extensive that we conclude that plaque and medial SMCs are distinctly different SMC cell types.

We characterized gene expression in plaque and medial SMC cultures developed from human carotid endarterectomy specimens. These cells were nearly indistinguishable by morphological features, population doubling time, and sensitivity to cell death induced by Fas cross-linking. Surprisingly, array expression analysis identified differences so extensive that we conclude that plaque and medial SMC are distinctly different SMC cell types.

Key Words: cell biology • genomics • gene expression • gene regulation

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