Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes involved in plaque rupture. Human coronary artery endothelial cells (ECs) were stimulated in vitro for 12 hours with plasma obtained from the coronary sinus (CS) and the aorta (Ao) of patients with ACS (n=8), or patients with stable angina (SA, n=4). For each patient, gene expression profile was evaluated by microarray technology in ECs exposed to plasma obtained from CS and compared to that of ECs exposed to plasma sampled from Ao. In patient with ACS we found 684 genes up-regulated and 283 down-regulated was observed as compared to patients with SA. Functional and network analyses of statistically significant gene showed that the up regulated genes were associated to pathways IL17 Signaling. To validate the microarray data the RNAs were used for Real Time PCR experiment. Human coronary artery endothelial cells (ECs) were stimulated in vitro for 12 hours with plasma obtained from the coronary sinus (CS) and the aorta (Ao) of patients with ACS (n=8), or patients with stable angina (SA, n=4). For each patient, gene expression profile was evaluated by microarray technology in ECs exposed to plasma obtained from CS and compared to that of ECs exposed to plasma sampled from Ao.
Project description:Transcriptome analysis of Peripheral Blood Mononuclear Cells (PBMC) samples from nine participants, including three in the Ctrl group, three in the (stable angina) SA group, and three in the acute coronary syndrome (ACS) group, was performed.
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes involved in plaque rupture. Human coronary artery endothelial cells (ECs) were stimulated in vitro for 12 hours with plasma obtained from the coronary sinus (CS) and the aorta (Ao) of patients with ACS (n=8), or patients with stable angina (SA, n=4). For each patient, gene expression profile was evaluated by microarray technology in ECs exposed to plasma obtained from CS and compared to that of ECs exposed to plasma sampled from Ao. In patient with ACS we found 684 genes up-regulated and 283 down-regulated was observed as compared to patients with SA. Functional and network analyses of statistically significant gene showed that the up regulated genes were associated to pathways IL17 Signaling. To validate the microarray data the RNAs were used for Real Time PCR experiment.
Project description:Coronary artery disease (CAD) remains a leading cause of death worldwide. Acute coronary syndromes (ACS) are the spectrum of diseases arising from coronary atherosclerotic plaque rupture, ranging from unstable angina (UA; clinical symptoms of cardiac ischemia without myocardial necrosis) to myocardial infarction (MI; clinical symptoms of cardiac ischemia with myocardial necrosis). We use microrray to identify changes in pathways following MI.This study examines mRNA expression levels in human whole blood at 7 and 30 days post ACS. Patients with MI are compared to those with UA (not healthy controls), thus focusing on differences in mRNA expression due to the acute clinical events rather than underlying atherosclerosis and its treatment.
Project description:Upon activation, platelets release a host of soluble and vesicular signals, collectively termed the ‘platelet releasate’ (PR). The contents of this PR play a significant role in haemostasis, inflammation, and pathologic sequelae. Despite this, proteomic studies investigating the PR in coronary artery disease have not been performed. We undertook a comparative label-free quantitative (LFQ) proteomic profiling of the 1U/ml thrombin-induced PR from 13 acute coronary syndrome (ACS-STEMI) versus 14 stable angina pectoris patients using a tandem mass spectrometry approach. We identified differentially released platet proteins including tetranectin (CLEC3B), protein disulfide-isomerase-A3 (PDIA3), coagulation factor V (F5) and fibronectin (FN1). Strikingly, all 9 differential proteins were associated with the GO cellular component term ‘extracellular vesicle’ and reduced levels of EVs were detected in plasma of ACS-STEMI patients. Network analysis revealed 3 PR proteins either reduced (F5; FN1) or absent (CLEC3B) in ACS-STEMI patients, which are strongly connected to both the clotting cascade and major druggable targets on platelets. This moderated signature highlights the possible basis of platelet dysfunction in ACS-STEMI and may prove useful for non-invasive risk assessment of the progression of coronary artery disease.
Project description:Coronary artery disease (CAD) remains a leading cause of death worldwide. Acute coronary syndromes (ACS) are the spectrum of diseases arising from coronary atherosclerotic plaque rupture, ranging from unstable angina (UA; clinical symptoms of cardiac ischemia without myocardial necrosis) to myocardial infarction (MI; clinical symptoms of cardiac ischemia with myocardial necrosis). We use microrray to identify changes in pathways following MI.This study examines mRNA expression levels in human whole blood at 7 and 30 days post ACS. Patients with MI are compared to those with UA (not healthy controls), thus focusing on differences in mRNA expression due to the acute clinical events rather than underlying atherosclerosis and its treatment. We recruited 26 patients presenting with acute coronary syndromes (ACS); 8 with unstable angina (UA) and 18 with MI. Supplementary files: The files contain the combined values (for each group) of the single patients' expression levels, the fold changes and the significance levels associated. Gene expression levels were estimated using probabilistic models implemented in puma (Propagating Uncertainty in Microarray Analysis, bioconductor.org), which provide estimates for the variance and credibility interval for probe level errors of each transcript. FCs were calculated after combining gene expression values within groups using Bayesian hierarchical model, incorporating probe level errors into the variance estimate. Significance levels for differentially expressed genes were detected by calculating the probability of positive log ratio (PPLR). The higher is the probability the more confident is the estimate of that positive FC, conversely the lower is the probability the more confident is the estimate of that FC to be negative. This model was implemented in the pumaComb and pumaDE modules within puma. file1 = mRNA_MI_combday30_exprs file2 = mRNA_MI_combDay7_exprs
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:Acute coronary syndrome (ACS) is presented as a group of symptoms resulting from acute ischemia of the myocardium due to rupture of a coronary arterial plaque. It comprises different classes; unstable angina, STEMI and NSTEMI. The current cornerstones of ACS diagnosis are ECG, CK-MB and cardiac troponins however there are several limitations leading to evading early diagnosis and poor prognosis. This highlights the need for more sensitive and specific biomarkers for a better outcome. In this study,an initial screening set is RNA sequenced for retrieval of differentially expressed genes and miRNAs. Then, a microRNA-long non-coding RNA multi biomarker panel is retrieved via in silico data analysis related to PINK1/Parkin-induced mitophagy. This is followed by clinical validation of their expression in serum of ACS patients in comparison to non-cardiac chest pain patients and healthy volunteers via qRT-PCR.
Project description:Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Aberrant expression of Transfer RNA-derived small RNAs (tsRNA) contributed to various human disease. However, the clincal utility and biological function of tsRNA in ACS are largely unknown. High throughput sequencing revealed a landscape of novel sncRNAs in the human PBMCs. tsRNAs represented a characteristic expression pattern in responding to acute coronary syndrome; tRF-Gly-GCC-06 and tRF-Lys-CTT-02 were significantly up-regulated in patients with unstable angina(UA) and acute myocardial infarction(AMI). Both of the two tRFs demonstrated reasonable diagnostic accuracy for ACS detection. tRF-Gly-GCC-06 and tRF-Lys-CTT-02 upregulation were independent predictors of an increased risk of ACS. Both of the two tRFs expression levels show a significantly positive correlation with Gensini score.Our study identified novel tsRNA alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets.
Project description:Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Aberrant expression of Transfer RNA-derived small RNAs (tsRNA) contributed to various human disease. However, the clincal utility and biological function of tsRNA in ACS are largely unknown. High throughput sequencing revealed a landscape of novel sncRNAs in the human PBMCs. tsRNAs represented a characteristic expression pattern in responding to acute coronary syndrome; tRF-Gly-GCC-06 and tRF-Lys-CTT-02 were significantly up-regulated in patients with unstable angina(UA) and acute myocardial infarction(AMI). Both of the two tRFs demonstrated reasonable diagnostic accuracy for ACS detection. tRF-Gly-GCC-06 and tRF-Lys-CTT-02 upregulation were independent predictors of an increased risk of ACS. Both of the two tRFs expression levels show a significantly positive correlation with Gensini score.Our study identified novel tsRNA alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets.