Circulating transcriptome reveals markers of atherosclerosis

Willmar D. Patino, Omar Y. Mian, Ju Gyeong Kang, Satoaki Matoba, Linda D. Bartlett, Brenda Holbrook, Hugh H. Trout, Louis Kozloff, Paul M. Hwang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3423-3428
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - Mar 1 2005

Keywords

  • 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor
  • Finkel-Biskis-Jinkins osteosarcoma
  • High sensitivity C-reactive protein
  • Monocytes
  • Serial analysis of gene expression

ASJC Scopus subject areas

  • General

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