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Association of peripheral-blood transcriptome with prognostic markers of myocardial damage assessed by cardiovascular magnetic resonance after reperfused ST-elevation myocardial infarction

: Teren, A.; Eitel, I.; Beutner, F.; Kirsten, H.; Scholz, M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Thiele, H.

European Heart Journal 35 (2014), Supplement 1, S.483
ISSN: 0195-668X
European Society of Cardiology (ESC Congress) <2014, Barcelona>
Fraunhofer IZI ()

Purpose: Aim of the present study was to identify associations of global gene expression in peripheral blood mononuclear cells (PBMC) with established cardiovascular magnetic resonance (CMR) markers of myocardial damage and prognosis after ST-elevation myocardial infarction (STEMI).
Methods: We enrolled 100 patients with STEMI (70.0% men, age 60.8±11.9 years) after primary angioplasty within 12h after symptom-onset [median pain-toballoon time 237 min (IQR 150–376)]. After reperfusion [median time interval 19.5 hrs (IQR 15–25)] whole blood was collected to perform high throughput transcriptome analysis in isolated PBMC using Illumina HumanHT-12 v4 Expression BeadChips. Subsequently, T2-weighted, SSFP-CINE, and contrast-enhanced CMR was performed within one week after infarction to assess the left ventricle ejection fraction (MR-EF), the myocardial salvage index (MSI), and to visualize late microvascular obstruction in relation to the infarct size (late MO/IS).
Results: After pre-processing accounting for relevant confounders, expression levels of 9949 genes were analysed. Among these, expression of one gene involved in the regulation of protein stability correlated strongest with MR-EF [pvalue = 1.7x10-5; false discovery rate (FDR) <0.21]. Another four genes were associated with late MO/IS at a FDR <0.25 (corresponding to p<9.4x10-5). No relevant links were found for MSI. Considering the top-associated transcripts at a less stringent cut-off p-value, KEGG pathway and gene ontology enrichment analysis was performed. MR-EF was found to associate with genes involved in posttranslational protein modification (24-fold enrichment, p=3.0x10-3) and nucleoside metabolism (5-fold enrichment, p=2.0x10-2). Genes correlating with late MO/IS were linked with several immunomodulatory pathways including the cellular response to calcium ion (104-fold enrichment, p=2.0x10-4), and lymphocyte differentiation (10-fold enrichment, p=1.5x10-2).
Conclusion: We identified several candidate gene transcripts in association with CMR-predictors of prognosis after STEMI, providing potential targets for translational research strategies.