Similar Datasets
Project description:Coronary atherosclerosis results from the delicate interplay of genetic and exogenous risk factors, principally taking place in metabolic organs and the arterial wall. Here we show that 224 gene-regulatory coexpression networks (GRNs) identified by integrating genetic and clinical data from patients with (n = 600) and without (n = 250) coronary artery disease (CAD) with RNA-seq data from seven disease-relevant tissues in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study largely capture this delicate interplay, explaining >54% of CAD heritability. Within 89 cross-tissue GRNs associated with clinical severity of CAD, 374 endocrine factors facilitated inter-organ interactions, primarily along an axis from adipose tissue to the liver (n = 152). This axis was independently replicated in genetically diverse mouse strains and by injection of recombinant forms of adipose endocrine factors (EPDR1, FCN2, FSTL3 and LBP) that markedly altered blood lipid and glucose levels in mice. Altogether, the STARNET database and the associated GRN browser (http://starnet.mssm.edu) provide a multiorgan framework for exploration of the molecular interplay between cardiometabolic disorders and CAD.
| S-EPMC9583458 | biostudies-literature
Project description:A mechanistic framework for cardiometabolic and coronary artery disease
| PRJNA781115 | ENA
Project description:Elevated plasma cholesterol and Type 2 Diabetes (T2D) are associated with Coronary Artery Disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explored the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic and clinical data, we identified a Glucose and Lipid Determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impacted lipid and glucose levels in inverse directions. Experimental knockdown of one of the GLD network master regulators, Lanosterol Synthase (LSS), in mouse confirmed the inverse relationships to glucose and lipid levels as predicted by our model and provided mechanistic insights.
2020-09-01 | GSE157223 | GEO
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
2022-12-18 | PXD036800 | Pride
Project description:Background Coronary artery bypass graft (CABG) surgery represents the preferred revascularization strategy for most patients with diabetes and multivessel disease. We aimed to evaluate the role of optimized, perioperative cardiometabolic targets on long-term survival in patients who underwent CABG. Methods and Results Single-institution retrospective study was conducted in patients with diabetes who underwent CABG between January 2010 and June 2018. Demographic, surgical, and cardiometabolic determinants were identified during the perioperative period. Clinical characteristics and longitudinal survival outcomes data were obtained. A total of 1534 patients with CABG were considered for analysis and 1273 met inclusion criteria. The mean age of patients was 63.3 years (95% CI, 62.7-63.8 years), and most were men (65%) and Hispanic or Latino (47%). Comorbidities included hypertension (95%) and dyslipidemia (88%). In total, 490 patients (52%) had a low-density lipoprotein cholesterol level >70 mg/dL. Furthermore, 390 patients (31%) had uncontrolled systolic blood pressure >130 mm Hg. Last, only 386 patients (29%) had a hemoglobin A1c level between 6% and 7%. At 5 years, 121 patients (10%) died. Failure to achieve goal systolic blood pressure was associated with all-cause (hazard ratio [HR], 1.573; 95% CI, 1.048-2.362 [P=0.029]) and cardiovascular (HR, 2.023; 95% CI, 1.196-3.422 [P=0.009]) mortality at 5 years post-CABG. In contrast, prescription of a statin during the perioperative interval demonstrated a protective effect for all-cause (HR, 0.484; 95% CI, 0.286-0.819 [P=0.007]) and cardiovascular (HR, 0.459; 95% CI, 0.229-0.920 [P=0.028]) mortality. There was no association between achievement of low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein cholesterol, or hemoglobin A1c level goals and mortality risk at 5 years. Conclusions Among patients with diabetes, blood pressure control and statin therapy were the most important perioperative cardiometabolic survival determinants 5 years after CABG.
| S-EPMC9238596 | biostudies-literature
Project description:BackgroundEffective waiting list management and comprehensive prioritisation can provide timely delivery of appropriate services to ensure that the patient needs are met and increase equity in the provision of health services. We developed a prioritisation framework for patients in need of coronary artery angiography (CAA).MethodsWe used a multi-methods approach to elicit effective factors that affect CAA patient prioritisation. Qualitative data wase collected using semi-structured interviews with 15 experts. The final set of factors was selected using experts' consensus through modifed Delphi technique. The framework was finalised during expert panel meetings.Results212 effective factors were identified based on the literature review, interviews, and expert panel discussion of them, 37 factors were selected for modifed Delphi study. Following two rounds of Delphi discussions, seven final factors were selected and weighed by ten experts using pair-wise comparisons. The following weights were given: the severity of pain and symptoms (0.22), stress testing (0.18), background diseases (0.15), number of myocardial infarctions (0.15), waiting time (0.10), reduction of economic and social performance (0.12), and special conditions (0.08).ConclusionClinical effective factors were important for CAA prioritisation framework. Using this framework can potentially lead to improved accountability and justice in the health system.
| S-EPMC8565640 | biostudies-literature
Project description:ObjectiveThis study focuses on the innovative application of Automated Machine Learning (AutoML) technology in cardiovascular medicine to construct an explainable Coronary Artery Disease (CAD) prediction model to support the clinical diagnosis of CAD.MethodsThis study utilizes a combined data set of five public data sets related to CAD. An ensemble model is constructed using the AutoML open-source framework AutoGluon to evaluate the feasibility of AutoML in constructing a disease prediction model in cardiovascular medicine. The performance of the ensemble model is compared against individual baseline models. Finally, the disease prediction ensemble model is explained using SHapley Additive exPlanations (SHAP).ResultsThe experimental results show that the AutoGluon-based ensemble model performs better than the individual baseline models in predicting CAD. It achieved an accuracy of 0.9167 and an AUC of 0.9562 in 4-fold cross-bagging. SHAP measures the importance of each feature to the prediction of the model and explains the prediction results of the model.ConclusionThis study demonstrates the feasibility and efficacy of AutoML technology in cardiovascular medicine and highlights its potential in disease prediction. AutoML reduces the barriers to model building and significantly improves prediction accuracy. Additionally, the integration of SHAP enhances model transparency and explainability, which is critical to ensuring model credibility and widespread adoption in cardiovascular medicine.
| S-EPMC11246996 | biostudies-literature
Project description:Study of atherosclerosis using 51 human coronary artery segments Keywords: other
2005-06-30 | GSE2143 | GEO
Project description:Here, we evaluated the appearance and abundance of Multinucleated varian endothelial cells after prolonged exposure (9 days) to high-glucose and high-insulin and characterized their morphology, as well as their mitochondrial mass and function. In addition, we performed a quantitative proteomic differential analysis among endothelial cells cultured under normal-glucose and high glucose+high-insulin.
2022-08-11 | PXD013643 | Pride
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
2003-10-28 | GSE616 | GEO