Document Detail

Suppression of inflammatory signaling in monocytes from patients with coronary artery disease.
MedLine Citation:
PMID:  19059264     Owner:  NLM     Status:  MEDLINE    
Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without angiographic signs of CAD. All patients were on statin and aspirin treatment. Elevated soluble-ICAM levels demonstrated increased vascular inflammation in atherosclerotic patients. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, and macrophages was subjected to genome-wide expression analysis. In CD14+ monocytes, few inflammatory genes were overexpressed in control patients, while atherosclerotic patients showed overexpression of a group of Krüppel-associated box - containing transcription factors involved in negative regulation of gene expression. These differences disappeared upon LPS-stimulation or differentiation towards macrophages. No consistent changes in T cell transcriptomes were detected. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers, while monocyte gene expression signature predicted patient status with an accuracy of 84%. In this comprehensive analysis of circulating cell transcriptomes in atherosclerotic CAD, cautious patient matching revealed only small differences in transcriptional activity in different mononuclear cell types. Only an indication of a negative feedback to inflammatory gene expression was detected in atherosclerotic patients. Transcriptome differences of circulating cells possibly play less of a role than hitherto thought in the individual patient's susceptibility to atherosclerotic CAD, when appropriately matched for clinical symptoms and medication taken.
Stephan H Schirmer; Joost O Fledderus; Anja M van der Laan; Tineke C T M van der Pouw-Kraan; Perry D Moerland; Oscar L Volger; Josefien M Baggen; Michael Böhm; Jan J Piek; Anton J G Horrevoets; Niels van Royen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-14
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  46     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-16     Completed Date:  2009-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  177-85     Citation Subset:  IM    
Department of Cardiology, Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.
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MeSH Terms
Antigens, CD14 / immunology
CD4-Positive T-Lymphocytes / immunology,  metabolism
Case-Control Studies
Coronary Angiography
Coronary Artery Disease / immunology*,  metabolism
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gene Expression / genetics
Intercellular Adhesion Molecule-1 / metabolism
Interleukin-10 / metabolism
Lipopolysaccharides / pharmacology
Middle Aged
Monocytes / drug effects,  immunology*,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Reg. No./Substance:
0/Antigens, CD14; 0/Lipopolysaccharides; 126547-89-5/Intercellular Adhesion Molecule-1; 130068-27-8/Interleukin-10

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