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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2000-2006.
Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-08-3283.


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Submitted August 26, 2004
Accepted October 28, 2004

High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells

Stephanie Bezzina Wettinger, Carine J Doggen, C A Spek, Frits R Rosendaal, and Pieter H Reitsma*

Laboratory for Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands; Laboratory of Molecular Genetics, Present address: University of Malta, Msida, Malta
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
Laboratory for Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands

* Corresponding author; email: p.h.reitsma{at}amc.uva.nl.

Background Studies on the role of inflammation in cardiovascular disease focus on surrogate markers like plasma levels of C-reactive protein or interleukins which are affected by several factors. In this study we employ an approach in which the inflammatory mRNA profile of leucocytes is measured directly in a multigene system. Methods and Results We investigated the mRNA profile for 35 inflammatory markers in blood samples in a case-control study including 524 men with a history of myocardial infarction and 628 control subjects. Compared to controls, patients showed mRNA profiles with increased levels of most inflammatory mRNAs. The two most prominent mRNA risk indicators encoded the secreted protein macrophage migration inhibitory factor (crude odds ratio (OR) 3.4 for the highest quartile versus the lowest quartile (95 percent confidence interval (CI95):2.3-4.9)), and the intracellular regulator proteinase inhibitor 9 (OR 2.5 for the highest versus the lowest quartile (CI95:1.8-3.5), both showing an increase in odds ratio with increasing quartiles. Conclusions Leucocytes in the blood of patients with myocardial infarction are more active in transcription of inflammatory genes, as evidenced by mRNA profiling. These data support the hypothesis that an inflammatory response involving leucocytes plays a role in the pathogenesis of myocardial infarction.


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