title: Circulating transcriptome reveals markers of atherosclerosis.
abstract: Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the in vivo transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel-Biskis-Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein. In vitro inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases.
authors.affiliation: Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10-CRC, 5 East, Room 5-5330, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Willmar D
authors.initials: WD
authors.lastname: Patino
authors.forename: Omar Y
authors.initials: OY
authors.lastname: Mian
authors.forename: Ju-Gyeong
authors.initials: JG
authors.lastname: Kang
authors.forename: Satoaki
authors.initials: S
authors.lastname: Matoba
authors.forename: Linda D
authors.initials: LD
authors.lastname: Bartlett
authors.forename: Brenda
authors.initials: B
authors.lastname: Holbrook
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Trout
authors.forename: Louis
authors.initials: L
authors.lastname: Kozloff
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hwang
mesh_terms: D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D012269:Ribosomal Proteins; C076845:FAU protein, human
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