High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of
Stephanie Bezzina Wettinger1, Carine J M Doggen, C Arnold Spek
1Laboratory for Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
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.
Insights
This study reveals that white blood cells in myocardial infarction patients exhibit heightened inflammatory gene activity. Key indicators include elevated messenger RNA for macrophage migration inhibitory factor and proteinase inhibitor 9, suggesting inflammation
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- Traditional cardiovascular disease inflammation markers are influenced by multiple factors.
- Direct measurement of inflammatory gene expression in leukocytes offers a more precise approach.
Purpose of the Study:
- To investigate the inflammatory mRNA profile of leukocytes in myocardial infarction patients.
- To identify specific inflammatory genes associated with myocardial infarction risk.
Main Methods:
- A case-control study involving 524 men with myocardial infarction and 628 controls.
- Analysis of mRNA profiles for 35 inflammatory markers in blood leukocytes using a multigene system.
Main Results:
- Patients with myocardial infarction showed increased mRNA levels for most inflammatory markers compared to controls.
- Elevated messenger RNA (mRNA) for macrophage migration inhibitory factor and proteinase inhibitor 9 were the strongest indicators of risk.
- A dose-response relationship was observed, with higher mRNA levels correlating with increased risk.
Conclusions:
- Leukocytes in myocardial infarction patients display enhanced inflammatory gene transcription.
- These findings support the role of leukocyte-mediated inflammation in the pathogenesis of myocardial infarction.
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