Circulating Transcriptome Reveals Markers of Atherosclerosis

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 t...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 9; pp. 3423 - 3428
Main Authors Patino, Willmar D., Mian, Omar Y., Kang, Ju-Gyeong, Matoba, Satoaki, Bartlett, Linda D., Holbrook, Brenda, Trout, Hugh H., Kozloff, Louis, Hwang, Paul M., Vogelstein, Bert
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 01.03.2005
National Acad Sciences
Subjects
Arteriosclerosis - blood
Arteriosclerosis - genetics
Atherosclerosis
Biological Sciences
Blotting, Western
Case-Control Studies
Cell adhesion
Cell lines
Comparative analysis
Coronary vessels
Gene expression
Genes
Humans
Immunohistochemistry
Libraries
Macrophages
Medical research
Monocytes
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Proteins - genetics
RNA, Messenger - blood
Small interfering RNA
Surgery
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 14
ObjectType-Article-2
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
Author contributions: W.D.P., J.-G.K., S.M., and P.M.H. designed research; W.D.P., O.Y.M., J.-G.K., S.M., L.D.B., B.H., H.H.T., L.K., and P.M.H. performed research; W.D.P., O.Y.M., J.-G.K., S.M., and P.M.H. analyzed data; and W.D.P. and P.M.H. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Edited by Bert Vogelstein, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
Abbreviations: SAGE, serial analysis of gene expression; hsCRP, high sensitivity C-reactive protein; statin, 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor; MNC, mononuclear cells; siRNA, small interfering RNA; CEA, carotid endarterectomy; FOS, Finkel–Biskis–Jinkins osteosarcoma; Ct, cycle threshold; PMA, phorbol 12-myristate 13-acetate; MCP-1, monocyte chemoattractant protein 1; DUSP1, dual specificity phosphatase 1.
To whom correspondence should be addressed. E-mail: hwangp@mail.nih.gov.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0408032102