Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.
Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10-5), and regulation of inflammatory response (p = 1.86 × 10-3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.
Department of Cardiology/Internal Medicine, Heart Center, University of Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany.
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Teren
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Medical Informatics, Statistic and Epidemiology, University of Leipzig, Germany.|IZI, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.
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Kirsten
Department of Cardiology/Internal Medicine, Heart Center, University of Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany.
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Beutner
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Medical Informatics, Statistic and Epidemiology, University of Leipzig, Germany.
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Scholz
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Laboratory Medicine, University Hospital Munich (LMU) and Ludwig-Maximilian- University Munich, Germany.
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Holdt
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Laboratory Medicine, University Hospital Munich (LMU) and Ludwig-Maximilian- University Munich, Germany.
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Teupser
Department of Diagnostic and Interventional Radiology, Heart Center, University of Leipzig, Germany.
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Gutberlet
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.|Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany.
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Thiery
Department of Cardiology/Internal Medicine, Heart Center, University of Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.
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Schuler
University Heart Center Lübeck, University of Lübeck, Medical Clinic II (Cardiology, Angiology and Intensive Care Medicine), Lübeck, Germany.
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Eitel
D015906:Angioplasty, Balloon, Coronary; D015415:Biomarkers; D004562:Electrocardiography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006334:Heart Function Tests; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging / Q000379:methods; D011379:Prognosis; D000072657:ST Elevation Myocardial Infarction / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D059467:Transcriptome
D015415:Biomarkers