Project description:To further development of our gene expression approach to biodosimetry, We through the detection of circular RNA (circRNA) using expression profiling chips, we searched for circRNAs related to acute myocardial infarction (AMI) and explored their relationship and possible mechanisms with AMI. The study subjects included 3 AMI patients and 3 controls, and circRNA expression profiling analysis was performed using a microarray gene chip to identify circRNAs with large differences in expression between groups and to construct a circRNA-microRNA (circRNA-miRNA) network.
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:In this study we aim to evaluate the diagnostic value of miRNAs for in the detection of acute myocardial infarction (AMI). We used microRNA microarray to screen differentially expressed microRNAs (miRNAs) in rat myocardial infarcted tissues compared with healthy control tissues. Then the expression of these miRNAs was further verified by quantitative real-time polymerase chain reaction (RT-PCR) in rat myocardial infarcted tissues and plasma. Finally, the diagnostic value of these circulating miRNAs was explored in 44 patients with AMI, 53 with coronary heart disease (CHD) and 56 healthy controls.
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.
Project description:Acute myocardial infarction (AMI) is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression (GE) profiling at the time of an AMI provides information concerning the platelet GE preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet GE identified five differentially expressed genes (DEGs): FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the GE in a STEMI vs healthy donors score showed an AUC of 0.95. The same five DEGs were externally validated using platelet GE data from patients with coronary atherosclerosis but without thrombosis. Early signals of an imminent AMI are likely to be found by platelet GE profiling before the infarction occurs.
Project description:Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. MicroRNAs (miRNAs) shape the transcript repertoire and control cellular functions. Imprecise cleavage of miRNA hairpins during biogenesis and downstream enzymatic processing alters mature miRNA arm abundance. Using small and total RNA sequencing, miRNA temporal dynamics and regulatory effects were studied in four cell types of the heart upon myocardial infarction. We define differentially processed miRNAs, which have changes in their arm ratios and have effects on target gene regulation. The identified miRNA subsets are enriched in templated isomiR modifications and show associations with RNA binding proteins, biogenesis and other processing factors. Our analysis reveals antagonistic functions co-regulated by the processed miRNA arms, beyond known pathways involved in cardiac regeneration. This study highlights novel insights into disease mechanisms controlled by dysregulated microRNA processing concerning acute damage response as well as long-time adaptation after AMI.
Project description:Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. MicroRNAs (miRNAs) shape the transcript repertoire and control cellular functions. Imprecise cleavage of miRNA hairpins during biogenesis and downstream enzymatic processing alters mature miRNA arm abundance. Using small and total RNA sequencing, miRNA temporal dynamics and regulatory effects were studied in four cell types of the heart upon myocardial infarction. We define differentially processed miRNAs, which have changes in their arm ratios and have effects on target gene regulation. The identified miRNA subsets are enriched in templated isomiR modifications and show associations with RNA binding proteins, biogenesis and other processing factors. Our analysis reveals antagonistic functions co-regulated by the processed miRNA arms, beyond known pathways involved in cardiac regeneration. This study highlights novel insights into disease mechanisms controlled by dysregulated microRNA processing concerning acute damage response as well as long-time adaptation after AMI.
Project description:This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets. Objectives: Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction(AMI)
Project description:The presence and amount of the proteins within a plasma clot may influence clot properties, like susceptibility to fibrinolysis, however, the plasma clot proteome has not yet been extensively described. The aim of the study was to investigate the protein composition of clots prepared ex vivo from plasma of the peripheral blood of four patients with acute myocardial infarction (AMI) in two time points: in the acute ischemic phase and two months later during the standard therapy. Proteomic analysis revealed a total number of 62 proteins identified in all 8 samples grouping into several distinct functional clusters (e.g. cholesterol transporter activity, immunoglobulin binding and peptidase regulatory activity). The protein signatures of clots differed significantly depending on time after ACS, showing 30% greater variability in protein composition of the clots prepared in the plasma two months after the onset of AMI as compared to the clots generated at the time of admission to the hospital. Several proteins that could be involved in clot formation and resolution showed an interesting pattern of changes over time. For example α2-antiplasmin, which was robustly present in clots of all patients in acute phase of AMI, was detectable in lower abundance in only 2 clots prepared in plasma taken 8-12 weeks after AMI, whereas serotransferrin can be detected only in the clots prepared from plasma taken later during the therapy. In conclusion, we provided the first qualitative analysis of proteomes of fibrin clots generated ex vivo in plasma taken from patients with AMI showing differences in protein composition between clots generated in the acute ischemic phase and those prepared two months later. It might be hypothesized that differences involving several proteins of potential influence on within-clot fibrinolysis and clot stability may partially explain time-dependent changes in the clots structure and firmness in patients with AMI.
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)