Dataset Information

Single-nucleus transcriptomics of epicardial adipose tissue from female pigs reveals effects of exercise training on resident innate and adaptive immune cells

ABSTRACT: Coronary artery disease (CAD) is a leading cause of death in women. Although exercise mitigates CAD, the mechanisms by which exercise impacts epicardial adipose tissue (EAT) are unknown. We hypothesized that exercise promotes an anti-inflammatory microenvironment in EAT from female pigs. Female Yucatan pigs (n=7) were assigned to sedentary (SED) or exercise (EX) treatments and coronary arteries were occluded (O vs N) with an ameroid to mimic CAD. EAT was collected for bulk and single-nucleus transcriptomic sequencing (snRNA-seq). Clustering analysis revealed nine cell types in EAT with the fibroblast and macrophage populations predominantly from O-EX EAT and the T cell population predominantly from the N-EX EAT. Exercise upregulated G-protein coupled receptor, S100 family, and FAK pathways and downregulated the coagulation pathway. Exercise caused increased interaction between immune cells and endothelial and mesenchymal cells in the insulin-like growth factor pathway and between endothelial cells and other cell types except B cells in the platelet endothelial cell adhesion molecule pathway 1. Coronary occlusion impacted the largest number of genes in T and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-EX EAT. Sub-clustering of endothelial cells revealed that N-EX EAT separated from other treatments. In conclusion, exercise training increased interaction amongst immune and mesenchymal and endothelial cells in female EAT. Exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded coronary arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT from women.

ORGANISM(S): Sus scrofa

PROVIDER: GSE246709 | GEO | 2023/11/05

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:The biological functions of epicardial adipose tissue (EAT) remain largely elusive. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). Objectives of this study were to identify genes that are up- or down-regulated among three adipose tissues (AT), namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. Samples were collected from patients undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in all three AT depots of six men using the lllumina® HumanWG-6 v3.0 expression BeadChips. Twenty-two and 73 genes were up-regulated in EAT compared to mediastinal and subcutaneous AT, respectively. Ninety-four genes were down-regulated in EAT compared to subcutaneous adipose depot. However, none were significantly down-regulated in EAT compared to mediastinal fat. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (epicardial > mediastinal > subcutaneous). The results of ADORA1 and PTGDS were confirmed by qPCR in 25 biological replicates. Overall, the transcriptional profiles of EAT and MAT were similar compared to the subcutaneous compartment. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD. Samples of epicardial, mediastinal and subscutaneous adipose tissue were collected from the chest of 6 male patients undergoing coronary artery bypass grafting surgeries. The RNA was labeled and hybridized using a standard Illumina protocol (https://icom.illumina.com/Login?ReturnUrl=%2ficom%2fsoftware.ilmn%3fid%3d214&id=214). Three pairwise comparison among the three adipose tissue were made using significance analysis of microarrays.

Project description:While the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise-trained for 16-20 weeks (n=8) and a group that remained sedentary (n=8). We found that a total of 130 genes were up regulated and 84 genes down regulated in brachial artery endothelial cells with exercise training. In contrast, a total of 113 genes were up regulated and 31 genes down regulated in internal mammary artery endothelial cells (>1.5-fold and false discovery rate<15%). Although there was an overlap of 66 genes (59 up regulated and 7 down regulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise-trained for 16-20 weeks (n=8) and a group that remained sedentary (n=8). The arteries were taken from the same animals, and after quality assessment, so there were 29 total arrays (15 unique pigs), 14 with an array for both the brachial artery and the internal mammary artery (IMA), and the remaining 1 having only brachial. One pig had bad RNA quality and is missing from both IMA and brachical. Therefore, there were 15 IMA (7 SED, 8 EX) and 14 brachial arrays (7 SED, 7 EX) that were used in this study.

Dataset Information

Single-nucleus transcriptomics of epicardial adipose tissue from female pigs reveals effects of exercise training on resident innate and adaptive immune cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets