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Published Online
on May 13, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print May 13, 2004, doi: 10.1161/01.ATV.0000132401.12275.0c
A more recent version of this article appeared on July 1, 2004
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Submitted on April 20, 2004
Accepted on May 4, 2004

Atherosclerotic Plaque Smooth Muscle Cells Have a Distinct Phenotype

Eileen R. Mulvihill *; Jochen Jaeger ; Rimli Sengupta ; Walter L. Ruzzo ; Cecile Reimer ; Sheila Lukito ; and 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.

* To whom correspondence should be addressed. 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/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.




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