Project description:Genetic predisposition through F11R-single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles (F11R-SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both F11R-SNVs and sJAM-A are associated with worse prognosis for recurrent myocardial infarction in CAD patients. Platelet surface-associated JAM-A correlate with platelet activation markers in CAD patients. Activated platelets shed transmembrane-JAM-A, generating proinflammatory sJAM-A and JAM-A-bearing microparticles. Platelet transmembrane-JAM-A and sJAM-A as homophilic interaction partners exaggerate thrombotic and thrombo-inflammatory platelet monocyte interactions. Therapeutic strategies interfering with this homophilic interface may regulate thrombotic and thrombo-inflammatory platelet response in cardiovascular pathologies where circulatory sJAM-A levels are elevated.
Project description:We aimed to clarify the possible functional role of hsa_circ_0000563 in coronary artery disease. Therefore, the ChIRP-MS was conducted to explore the interaction between BTBD7_hsa_circ_0000563 and proteins on a genomic scale in human peripheral blood mononuclear cell (PBMC). This project is the raw files of the proteins bound to hsa_circ_0000563 found by ChIRP-MS in PBMC.
Project description:The human LncRNA microarray analysis of the 6 monocytes samples from Coronary Artery Disease patients and non Coronary Artery Disease 3 Coronary Artery Disease patients and 3 non-Coronary Artery Disease donors
Project description:The human LncRNA microarray analysis of the 6 plasma samples from Coronary Artery Disease patients and non Coronary Artery Disease Agilent Feature Extraction software (version 11.0.1.1) was used to analyze acquired array images. Quantile normalization was performed using Expander6 and subsequent data processing was performed using the GeneSpring GX v11.5.1 software package (Agilent Technologies). After low intensity filtering, LncRNAs and mRNAs that at least 2 out of 12 samples have flags in Present or Marginal (“All Targets Value”) were chosen for quantile normalization and further data analysis. Differentially expressed LncRNAs and mRNAs with statistical significance were identified through Volcano Plot filtering. Pathway analysis and GO analysis were applied to determine the roles of these differentially expressed mRNAs played in these biological pathways or GO terms. Finally, Hierarchical Clustering was performed to show the distinguishable LncRNAs expression pattern among samples.
Project description:We developed a coronary plaque sampling approach that could be applied broadly in live patients with coronary artery disease (CAD) to obtain molecular and cellular insights into human coronary atherosclerosis. Our approach combined RNA retrieval directly from balloons used in percutaneous coronary interventions (PCI) and inexpensive, low-input RNA-Seq using SMART-seq. We generated SMART-Seq libraries from coronary samples from 27 patients. Of the 27 patients, 13 were confirmed to have stable CAD (sCAD) and 14 confirmed to have been performed on lesions causing acute coronary syndrome (ACS). We applied CIBERSORTx to analyze the SMART-seq data from each of the 27 samples. We found fibroblasts and fibromyoctes were enriched, while smooth muscle cells were reduced, in samples from ACS compared with sCAD patients. We identified 371 genes as significantly differential expressed (q<0.05) between sCAD and ACS patients.
Project description:Purpose: Utilized Next-generation sequencing (NGS) to profile transcriptional differences between two populations, carriers (CC) of rs10846744 SNP associated with cardiovascular disease (CVD) and non-carriers (GG) who are disease free. Methods: Total RNA was isolated from three subjects homozygous for the rs10846744 reference (GG) allele and three subjects homozygous for the rs10846744 risk (CC) allele and then subjected to full transcriptome sequencing using the Perkin Elmer next gen sequencing platform (Perkin Elmer, Branford, CT). Bioinformatics was performed using Perkin Elmer GeneSifter software program. The data was adjusted by selecting total map reads, quality reads >20, log transformation, and using Benjamini Hochberg to correct for multiple testing. RNA targets of interest were validated by qRT–PCR using TaqMan assays and western blotting using standard methodologies. Results: Using Perkin Elmer's Genesifter Analysis Edition Software, we mapped about 100 million sequence reads per sample to the human genome (build 37.2), normalized the raw read count by total mapped million reads and identified 937 upregulated and 587 downregulated transcripts in the EBV (Epstein Barr Virus)-transformed B lymphocyte cells isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele with BWA workflow. RNA-seq data confirmed differential expression of LAG3 and this was validated with qRT–PCR. Conclusions: Our study represents the first detailed analysis of differential LAG3 expression, contributing to CVD, with biologic replicates, generated by RNA-seq technology.
Project description:The human LncRNA microarray analysis of the 6 monocytes samples from Coronary Artery Disease patients and non Coronary Artery Disease
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) and the frequently coexisting aortic valve stenosis (AS) are the heart diseases accounting for the highest proportion of cardiac surgeries. Routine biomarkers for an earl detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis and to evaluate their severity with imaging techniques before they become advanced to the point where intervention or surgery have limited therapeutic benefit. Urine is an attractive biofluid for biomarker assessment, provided the noninvasive nature of its collection. Therefore, we conducted a shotgun proteomics analysis of urine collected from 12 CAD and/or AS patients and 11 cardiovascular disease-free controls, aiming at identification of putative molecular candidates that could differentiate these diseases from healthy subjects