Project description:Aims. We sought for peripheral blood gene expression signatures at presentation that distinguish the ST elevation (STEMI) and non-ST elevation myocardial infarction (NSTEMI) conditions, to define a precise map of differentially regulated biological processes, unveil new distinctive traits, and help predict markers of outcome. Methods and results. Total RNA from whole blood of STEMI and NSTEMI patients was used to prepare poly(A)+ enriched libraries for paired-end RNA-Seq. Transcriptomes were reconstructed and, after adjustment for unwanted variation, we performed differential expression analysis. Enrichment analyses was performed to infer differentiating functional networks. We identified 153 differentially expressed genes, which stood correction for TnI levels at admission and included 32 putative novel genes (false discovery rate-adjusted P<0.05). We found a divergent modulation of inflammatory, immune-response, angiogenic, and mitochondrial dynamics pathways. Finally, we showed that specific gene expression patterns at admission predict troponin I (TnI) peak levels and/or GRACE risk score. Conclusions. RNA-Seq allowed identifying novel differentially expressed genes in STEMI vs. NSTEMI, which might uncover unappreciated mechanisms underlying acute MI. Overall, our results depicted a scenario characterizing different pathological traits of these two types of acute MI that could pave the way for the identification of novel, specific biomarkers for early diagnosis, risk stratification, and therapeutic decision-making.
Project description:We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI) We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: ST-elevation myocardial infarction (STEMI, n=7), Non-ST-elevation MI (NSTEMI, n=10) and unstable angina (UA, n=9), and normal control (n=7)
Project description:We aimed to confirm the different expression profiles of circular RNAs (circRNAs) between ST-elevation myocardial infarction (STEMI) and chronic coronary syndromes (CCS) and identify the role of circRNAs in STEMI.
Project description:Affymetrix microarray (GeneChip microRNA 4.0) profilling of circulating miRNAs. We used miRNA arrays to profile miRNAs isolated from plasma of ST-segment elevation acute myocardial infarction (STEMI)-patients with cardiogenic shock (CS) or without cariogenic shock (Non-CS)
Project description:We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI)
Project description:Rationale: Pro-angiogenic effects of mobilised bone-marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. Objective: To determine the differential regulation of angiomiRs, i.e microRNAs regulating neovascularisation, in mobilised CD34+ progenitor cells obtained from patients with an acute ST-segment elevation myocardial infarction (STEMI) as compared to those with stable coronary artery disease (sCAD) or healthy subjects. Methods and Results: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), sCAD and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased pro-angiogenic activity as compared to CD34+ cells from the other groups. Using a PCR-based miRNA-array and Real-Time PCR validation we identified a profound up-regulation of two known angio-miRs, i.e. miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the pro-angiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in-vitro and in-vivo, whereas let-7b up-regulation in CD34+ cells failed to proof its effect on endothelial cells in-vivo. Conclusion: The present study demonstrates for the first time a significant upregulation of the angiomiRs miR-378 and let-7b in mobilised CD34+ progenitor cells of patients with STEMI. The increased pro-angiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in-vivo suggest that this unique microRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.