Project description:Atherosclerosis is a major contributor to cardiovascular diseases. Well-established preclinical models that can accurately recapitulate human atherosclerosis development and progression are necessary for developing new therapeutics. Pig models are extensively used in cardiovascular research due to their physiological similarities to humans. However, their translational efficacy into clinical settings has remained limited. To ensure better translational outcomes, a deeper molecular characterization of atherosclerotic disease mechanisms in swine models is urgently required. Methods: To address this gap, we employed single nuclei transcriptomics to characterize healthy and atherosclerotic aortas in the Ossabaw pig model. We analyzed over 36,000 nuclei from aortas of 5 adult male castrated pigs kept on atherogenic and chow diets. In-depth single-nuclei transcriptomic and cell-cell communication analyses were undertaken to uncover molecular changes in swine atherosclerosis development. Comparisons to human and mouse atherosclerosis were used to establish the veracity of the Ossabaw pig in modeling human disease.
Project description:Overall diet quality and statin therapy are important modulators of inflammation and CAD progression, yet their effects on colon is not well understood. Our objective was to examine the effects and interaction of dietary patterns and statin therapy on colonic mucosa gene expression in the Ossabaw pig.
Project description:We investigated the effect of 2 food-based dietary patterns and statin therapy on the transcriptome of the left anterior descending coronary artery of the Ossabaw pig.
Project description:Epicardial adipose tissue (EAT) inflammation is thought to potentiate the development of coronary artery disease (CAD). Overall diet quality and statin therapy are important modulators of inflammation and CAD progression. Our objective was to examine the effects and interaction of dietary patterns and statin therapy on EAT gene expression in the Ossabaw pig.
Project description:To explore circRNAs expression profiles of mouse atherosclerotic model, we performed RNA-seq to detect circRNAs with potential functional role in atherosclerosis (AS).
Project description:Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD) relative to a heart-healthy diet (HHD) on microvessel transcriptomics and metabolomics of the brain temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were randomized to the WD or HHD starting at the age of 4 months and were fed the assigned diet for the following 6 months. The WD and HHD were isocaloric and had the same macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received a statin. Relative to HHD-fed pigs, WD-fed pigs had 2,172 genes differentially expressed (FDR<0.05) by diet, 796 upregulated and 1,376 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD, including cell energetics, neurotransmission, and inflammation resolution pathways. Enrichment in arginine, tyrosine, and lysine was observed in WD-fed pigs and enrichment in ergothioneine and S-adenosyl methionine in HHD-fed pigs. Statin treatment had very modest effects on brain vessel transcriptome. Our study suggests a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.
Project description:Overall diet quality and statin therapy are important modulators of inflammation and CAD progression, yet their effects on jejunum is not well understood. Our objective was to examine the effects and interaction of dietary patterns and statin therapy on jejunal mucosa gene expression in the Ossabaw pig.
Project description:Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is a hallmark of atherosclerotic diseases. We used single nuclei RNA sequencing (snRNA-seq) to analyze the impact of defective hepatic glutaminolysis on cell diversity in atherosclerotic aorta.