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A gene expression signature that classifies human atherosclerotic plaque by relative inflammation status.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Puig, Oscar Yuan, Jeffrey Stepaniants, Sergey Zieba, Renata Zycband, Emanuel Morris, Mark Coulter, Silvija Yu, Xiang Menke, John Woods, John Chen, Fabian Ramey, Dena R. He, Xuanmin O'Neill, Edward A. Hailman, Eric Johns, Douglas G. Hubbard, Brian K. Yee Lum, Pek Wright, Samuel D. Desouza, Mary M. Plump, Andrew Reiser, Vladimír
Description	Country affiliation: United States Author Affiliation: Puig O ( Department of Molecular Profiling,, Merck Research Laboratories, Rahway, NJ 07033, USA. oscar_puig@merck.com)
Abstract	BACKGROUND: Atherosclerosis is a complex disease requiring improvements in diagnostic techniques and therapeutic treatments. Both improvements will be facilitated by greater exploration of the biology of atherosclerotic plaque. To this end, we carried out large-scale gene expression analysis of human atherosclerotic lesions. METHODS AND RESULTS: Whole genome expression analysis of 101 plaques from patients with peripheral artery disease identified a robust gene signature (1514 genes) that is dominated by processes related to Toll-like receptor signaling, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction, and lysosomal activity. Further analysis of gene expression in microdissected carotid plaque samples revealed that this signature is differentially expressed in macrophage-rich and smooth muscle cell-containing regions. A quantitative PCR gene expression panel and inflammatory composite score were developed on the basis of the atherosclerotic plaque gene signature. When applied to serial sections of carotid plaque, the inflammatory composite score was observed to correlate with histological and morphological features related to plaque vulnerability. CONCLUSIONS: The robust mRNA expression signature identified in the present report is associated with pathological features of vulnerable atherosclerotic plaque and may be useful as a source of biomarkers and targets of novel antiatherosclerotic therapies.
File Format	HTM / HTML
ISSN	1942325X
e-ISSN	19423268
Journal	Circulation: Cardiovascular Genetics
Issue Number	6
Volume Number	4
Language	English
Publisher	American Heart Association
Publisher Date	2011-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cardiology Gene Expression Profiling Plaque, Atherosclerotic Genetics Immunology Biological Markers Macrophages Molecular Sequence Data Proteins Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical) Cardiology and Cardiovascular Medicine

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