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Atherosclerosis is a progressive disease characterized by the accumulation of lipids in the large and medium sized arteries. Lipoproteins and the endothelium play critical roles in the onset of atherosclerosis through the regulation of trans-endothelial lipoprotein flux in the subintima, the expression of adhesion molecules and proinflamatory cytokine, and the recruitment of monocytic precursors to intimal macrophage foam cells. Although it has been greatly studied in animal models, including rabbits, pigs, non-human primates and rodents, the early development of atherosclerosis is unknown. In this study, we characterized the temporal changes of carotid endothelial transcriptome in hyperlipidemic pigs using next-generation RNA sequencing. Twenty litters of castrated barrows swine (Yorkshire x Landrace) were raised on a normal diet. The swine (~250 lbs) were then fed with a diet high in fat and cholesterol (HFHC) for 0, 2, 4, 8, or 12 weeks (n=4 animals for each time point) prior to tissue collections. The normal diet consisted of a standard commercial corn/soybean meal diet (18% crude protein) at 100% ad libitum intake. The isocaloric high fat/high cholesterol diet consisted of 16.5% crude protein, 15% fat and 1.5% cholesterol at 80% of the ad libitum feed rate (by weight) such that the caloric intake/kg BW were approximately the same as the control diet. Diets were adjusted biweekly according to body weight. Food was withheld for 24 hours prior to endothelium collection in order to permits the collection of blood for fasting lipid levels. |