Project description:Heart failure (HF) is the most common cause of morbidity and mortality in the developed countries, especially considering the present demographic tendencies in those populations. We identified biologically relevant transcripts that are significantly altered in the early phase of myocardial infarction (MI) and are associated with the development of post-myocardial infarction HF. We collected peripheral blood samples from patients (n=111) with ST-segment elevation myocardial infarction (STEMI) at four time points (admission, discharge, 1 month after MI, and 6 months after MI). Control group comprised patients (n=46) with a stable coronary artery disease and without a history of myocardial infarction. Affymetrix HuGene 1.0 ST arrays were used to analyze mRNA levels in periperal blood mononuclear cells (PBMCs) isolated from the study and control groups. Samples from the first three time points were compared with the samples from the same patients collected 6 months after MI (stable phase) and with the control group. Additionaly, based on plasma NT-proBNP level and left ventricular ejection fraction parameters the STEMI patients were divided into HF and non-HF groups.We attempted to identify transcripts whose differential expression on the 1st day of myocardial infarction predicted which patients would develop symptoms of HF during the 6 months of follow-up. For this purpose, we compared the microarray results for samples collected on admission for the HF group versus the non-HF group.
Project description:Identifying novel candidate biomarker gene differentially expressed in the peripheral blood cells of patients with early stage acute myocardial infarction using microarray as a high throughput screening technology.
Project description:Analysis of peripheral blood specimens from patients with acute myocardial infarction (AMI). Results provide insight into molecular mechanisms associated with AMI.
Project description:Single cell sequencing in peripheral blood mononuclear cells (PBMCs) revealed a novel human-specific long noncoding RNA called heart-failure associated transcript 4 (HEAT4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction (AMI) and cardiogenic shock (CS). The transcriptional regulation of HEAT4 was verified through cytokine treatment and single cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA–protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB-17-Prkdc scid/Rj mice.
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:Inflammatory mechanisms and immune cells are involved in acute coronary syndromes (ACS) and may lead to acute plaque rupture. However, the local expression of the different genes potentially involved is largely unknown. We therefore performed an Affymetrix analysis of genes expressed in white blood cells obtained from an occluding coronary thrombus or peripheral blood of patients with ST-elevation myocardial infarction. Thrombi of ACS patients were harvested from the site of coronary occlusion. Leukocytes were isolated by Ficoll centrifugation. Peripheral blood leukocytes (PBL) were treated in a similar fashion and mRNA was extracted from both cells.
Project description:We studied new microRNAs involved in the left ventricular adverse remodeling (LVAR) process after the ST elevation myocardial infarction (STEMI). We analyzed the expression of miRNAs in peripheral blood mononuclear cells (PBMCs) isolated from a group of non-LVAR (n = 5) and LVAR STEMI patients (n = 5), before (0 hour) and after a primary percutaneous coronary intervention (PPCI; 6 hours).
Project description:Inflammatory mechanisms and immune cells are involved in acute coronary syndromes (ACS) and may lead to acute plaque rupture. However, the local expression of the different genes potentially involved is largely unknown. We therefore performed an Affymetrix analysis of genes expressed in white blood cells obtained from an occluding coronary thrombus or peripheral blood of patients with ST-elevation myocardial infarction.
Project description:Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC). We isolated circulating endothelial cells from patients experience acute myocardial infartion and healthy cohorts, and measured gene expression using the HG-133U_PLUS_2 microarray Circulating endothelial cells were isolated from patients experiencing acute myocardial infarction (n=49) and from healthy cohorts (n=50). The patients were separated into a discovery cohort (n=43) for biomarker discovery and model training; and into a validation cohort (n=56) for biomarker validation and model testing.
