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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:319.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Expression Profiling Identifies Smooth Muscle Cell Diversity Within Human Intima and Plaque Fibrous Cap

Loss of RGS5 Distinguishes the Cap

Lawrence D. Adams; Randolph L. Geary; Jing Li; Anthony Rossini; Stephen M. Schwartz

From the Department of Pathology (L.D.A., S.M.M.), Center for Cardiovascular Biology and Regenerative Medicine, and the Department of Biostatistics (A.R.), University of Washington School of Medicine, Seattle; and the Division of Surgical Sciences (R.L.G., J.L.), Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Lawrence Adams, University of Washington, Department of Pathology, 815 Mercer St # 419, Seattle, WA 98109-4714. E-mail ladams{at}u.washington.edu

Background— The fibrous cap of the atherosclerotic lesion is believed to be critical to stability because disruption of the cap is the final event leading to plaque rupture. We have, therefore, used expression arrays to define the phenotype of the cap and other plaque components.

Methods and Results— To identify unique expression programs able to distinguish the smooth muscle of the cap from other plaque smooth muscle cells, RNA profiles were determined in human carotid artery media, nonatherosclerotic adjacent intima, fibrous cap of advanced atherosclerotic plaques, and whole advanced plaque with cDNA arrays covering 21 000 or 26 000 Unigene clusters. The molecular signature of each tissue was dominated by a core gene-set with differential expression of <1% of clusters assayed.

Conclusions— Both intima and cap expressed novel genes not previously associated with SMC pathology. If the cap is derived from a unique subpopulation, this pattern is the signature of that particular set of cells. The loss of RGS5 in the fibrous cap is of particular interest because of its role in vessel development and physiology.

Expression profiles of whole plaque and plaque subcomponents (media; adjacent nonatherosclerotic intima; and fibrous cap) were obtained on filter sets containing 21 000 or 26 000 Unigene clusters. Unique patters of gene expression characterized each layer. One remarkable difference was the loss of RGS5 expression in the fibrous cap compared with adjacent nonatherosclerotic intima and media.

Key Words: atherosclerosis • cardiovascular diseases • genes • molecular biology • plaque

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