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


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.
Department of Molecular Profiling,, Merck Research Laboratories, Rahway, NJ 07033, USA. oscar_puig@merck.com
Oscar
O
Puig
Jeffrey
J
Yuan
Sergey
S
Stepaniants
Renata
R
Zieba
Emanuel
E
Zycband
Mark
M
Morris
Silvija
S
Coulter
Xiang
X
Yu
John
J
Menke
John
J
Woods
Fabian
F
Chen
Dena R
DR
Ramey
Xuanmin
X
He
Edward A
EA
O'Neill
Eric
E
Hailman
Douglas G
DG
Johns
Brian K
BK
Hubbard
Pek
P
Yee Lum
Samuel D
SD
Wright
Mary M
MM
Desouza
Andrew
A
Plump
Vladimír
V
Reiser
D015415:Biomarkers; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; D011506:Proteins