title: High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells.
abstract: Studies on the role of inflammation in cardiovascular disease focus on surrogate markers like plasma levels of C-reactive protein or interleukins that 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. 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 with controls, patients showed mRNA profiles with increased levels of most inflammatory mRNAs. The 2 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% 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. 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.
authors.affiliation: Laboratory for Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Stephanie Bezzina
authors.initials: SB
authors.lastname: Wettinger
authors.forename: Carine J M
authors.initials: CJ
authors.lastname: Doggen
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Reitsma
mesh_terms: D000328:Adult; D000368:Aged; D001773:Blood Cells; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D015843:Serpins / Q000235:genetics; D015854:Up-Regulation
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D015843:Serpins