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Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Papio hamadryas Homo sapiens

PROVIDER: GSE139981 | GEO | 2022/07/10

REPOSITORIES: GEO

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Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [LCLF]

Project description:Analysis of hepatic transcript data using unbiased Weighted Gene Correlation Network Analysis (WGCNA) to identify significant modules of genes correlated with lesion burden and performed pathway enrichment analysis of genes in significant modules. The hypothesis tested in the present study was that transcript modules are predictive of atherosclerotic lesion burden after a high cholesterol, high fat diet challenge. Results of the study provide an understanding of the key pathways and genes underlying atherosclerotic lesion burdenafter high cholesterol and high fat diet challenge in baboons .

2022-07-10 | GSE139976 | GEO

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [7weeks HCHF]

Project description:Analysis of hepatic transcript data using unbiased Weighted Gene Correlation Network Analysis (WGCNA) to identify significant modules of genes correlated with lesion burden and performed pathway enrichment analysis of genes in significant modules. The hypothesis tested in the present study was that transcript modules are predictive of atherosclerotic lesion burden after a high cholesterol, high fat diet challenge. results of the study provide an understanding of the key pathways and genes underlying atherosclerotic lesion burdenafter high cholesterol and high fat diet challenge in baboons .

2022-07-10 | GSE139978 | GEO

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [2 years HCHF]

Project description:Analysis of hepatic transcript data using unbiased Weighted Gene Correlation Network Analysis (WGCNA) to identify significant modules of genes correlated with lesion burden and performed pathway enrichment analysis of genes in significant modules. The hypothesis tested in the present study was that transcript modules are predictive of atherosclerotic lesion burden after a high cholesterol, high fat diet challenge. results of the study provide an understanding of the key pathways and genes underlying atherosclerotic lesion burdenafter high cholesterol and high fat diet challenge in baboons .

2022-07-10 | GSE139979 | GEO

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons

Project description:Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons

| PRJNA587774 | ENA

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [LCLF]

Project description:Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [LCLF]

| PRJNA587776 | ENA

Hepatic transcript signatures predict atherosclerotic lesion burden prior to a 2-year high cholesterol, high fat diet challenge.

Project description:The purpose of this study was to identify molecular mechanisms by which the liver influences total lesion burden in a nonhuman primate model (NHP) of cardiovascular disease with acute and chronic feeding of a high cholesterol, high fat (HCHF) diet. Baboons (47 females, 64 males) were fed a HCHF diet for 2 years (y); liver biopsies were collected at baseline, 7 weeks (w) and 2y, and lesions were quantified in aortic arch, descending aorta, and common iliac at 2y. Unbiased weighted gene co-expression network analysis (WGCNA) revealed several modules of hepatic genes correlated with lesions at different time points of dietary challenge. Pathway and network analyses were performed to study the roles of hepatic module genes. More significant pathways were observed in males than females. In males, we found modules enriched for genes in oxidative phosphorylation at baseline, opioid signaling at 7w, and EIF2 signaling and HNF1A and HNF4A networks at baseline and 2y. One module enriched for fatty acid β oxidation pathway genes was found in males and females at 2y. To our knowledge, this is the first study of a large NHP cohort to identify hepatic genes that correlate with lesion burden. Correlations of baseline and 7w module genes with lesions at 2y were observed in males but not in females. Pathway analyses of baseline and 7w module genes indicate EIF2 signaling, oxidative phosphorylation, and μ-opioid signaling are possible mechanisms that predict lesion formation induced by HCHF diet consumption in males. Our findings of coordinated hepatic transcriptional response in male baboons but not female baboons indicate underlying molecular mechanisms differ between female and male primate atherosclerosis.

| S-EPMC9352111 | biostudies-literature

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [7weeks HCHF]

Project description:Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [7weeks HCHF]

| PRJNA587777 | ENA

Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [2 years HCHF]

Project description:Hepatic transcript modules are predictive of atherosclerotic lesion burden after a 2-year high cholesterol, high fat diet challenge in baboons [2 years HCHF]

| PRJNA587778 | ENA

Atherosclerotic lesion-specific copper delivery suppresses atherosclerosis in high-cholesterol-fed rabbits.

Project description:Dietary cholesterol supplements cause hypercholesterolemia and atherosclerosis along with a reduction of copper concentrations in the atherosclerotic wall in animal models. This study was to determine if target-specific copper delivery to the copper-deficient atherosclerotic wall can block the pathogenesis of atherosclerosis. Male New Zealand white rabbits, 10-weeks-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as control. Twelve weeks after the feeding, the animals were injected with copper-albumin microbubbles and subjected to ultrasound sonication specifically directed at the atherosclerotic lesions (Cu-MB-US) for target-specific copper delivery, twice a week for four weeks. This regiment was repeated 3 times with a gap of two weeks in between. Two weeks after the last treatment, the animals were harvested for analyses of serum and aortic pathological changes. Compared to controls, rabbits fed cholesterol-rich diet developed atherosclerotic lesion with a reduction in copper concentrations in the lesion tissue. Cu-MB-US treatment significantly increased copper concentrations in the lesion, and reduced the size of the lesion. Furthermore, copper repletion reduced the number of apoptotic cells as well as the content of cholesterol and phospholipids in the atherosclerotic lesion without a disturbance of the stability of the lesion. The results thus demonstrate that target-specific copper supplementation suppresses the progression of atherosclerosis at least in part through preventing endothelial cell death, thus reducing lipid infiltration in the atherosclerotic lesion.

| S-EPMC8669168 | biostudies-literature

Genetic regulatory effects in response to a high cholesterol, high fat diet in baboons.

Project description:Steady-state expression quantitative trait loci (eQTLs) explain only a fraction of disease-associated loci identified through genome-wide association studies (GWAS), while eQTLs involved in gene-by-environment (GxE) interactions have rarely been characterized in humans due to experimental challenges. Using a baboon model, we found hundreds of eQTLs that emerge in adipose, liver, and muscle after prolonged exposure to high dietary fat and cholesterol. Diet-responsive eQTLs exhibit genomic localization and genic features that are distinct from steady-state eQTLs. Furthermore, the human orthologs associated with diet-responsive eQTLs are enriched for GWAS genes associated with human metabolic traits, suggesting that context-responsive eQTLs with more complex regulatory effects are likely to explain GWAS hits that do not seem to overlap with standard eQTLs. Our results highlight the complexity of genetic regulatory effects and the potential of eQTLs with disease-relevant GxE interactions in enhancing the understanding of GWAS signals for human complex disease using nonhuman primate models.

| S-EPMC10418186 | biostudies-literature

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