Temporal adaptation of carotid endothelial transcriptome in hyperlipidemic pigs
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ABSTRACT: 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.
Project description: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, little is known about the regression of the disease. There are beneficial effects seen clinically in modification of diet and blood lipid. To determine the effect of withdrawl of risk factors (diet) on endothelial gene expression, in this study we characterized the temporal changes of carotid endothelial transcriptome in hyperlipidemic pigs using next-generation RNA sequencing. Ten 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). One cohort (5 animals) was on HFHC for 20 weeks prior to tissue collections. Another cohort (5 animals) was on HFHC for 12 weeks and then on a normal diet (ND) for 8 weeks. The normal diet consisted of a standard commercial corn/soybean meal diet (18% crude protein) at 100% ad libitum intake. The isocaloric HFHC 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 permit the collection of blood for fasting lipid levels.
Project description:Atherosclerosis preferentially develops in susceptible regions of the arterial system that are defined by the regional vascular hemodynamics. Previous work in adult castrate male pigs revealed the coexistence of pro- and anti-atherosclerotic profiles in endothelial cell gene expression in disturbed flow regions of arteries in the absence of risk factors for atherogenesis. This study investigates the impact of gender, high fat/high cholesterol diet and regional hemodynamics on arterial endothelial cell gene expression profiles in sexually mature intact pigs.
Project description:Transcriptional profiling in peritoneal adipose tissue of 48 pigs (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated. Four experimental groups: low-RFI pigs fed high fat, high fiber diet (HF_RFIneg), high-RFI pigs fed high fat, high fiber diet(HF_RFIpl), low-RFI pigs fed low fat, low fiber diet (LF_RFIneg) and high-RFI pigs fed low fat, low fiber diet(LF_RFIpl). 12 pigs per condition. One replicate per array.
Project description:Transcriptional profiling in subcutaneous adipose tissue of 48 pigs aged (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated. Four experimental groups: low-RFI pigs fed high fat, high fiber diet (HF_RFIneg), high-RFI pigs fed high fat, high fiber diet(HF_RFIpl), low-RFI pigs fed low fat, low fiber diet (LF_RFIneg) and high-RFI pigs fed low fat, low fiber diet(LF_RFIpl). 12 pigs per condition. One replicate per array.
Project description:Transcriptional profiling in the whole blood of 48 pigs (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated. Four experimental groups : low-RFI pigs fed high fat, high fiber diet (HF_RFIneg), high-RFI pigs fed high fat, high fiber diet(HF_RFIpl), low-RFI pigs fed low fat, low fiber diet (LF_RFIneg) and high-RFI pigs fed low fat, low fiber diet(LF_RFIpl). 12 pigs per condition. One replicate per array.
Project description:The objective of the experiment was to dissect the effects of a high-fat diet on juvenile adipose tissue gene expression under conditions of excess calorie intake versus normal calorie intake in comparison to a standard low-fat diet. For this purpose juvenile mice were fed (A) a standard low-fat diet (CD), (B) a high-fat diet ad libitum (excess calorie intake) (HFD) and (C) a high-fat diet with calorie consumption restricted to the calorie consumption of the CD diet (R-HFD). RNA expression was profiled after 1 week of feeding in the periuterine fat depot.
Project description:Transcriptional profiling in skeletal muscle of 48 pigs (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated.
Project description:Transcriptional profiling in liver of 48 pigs (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated.
Project description:Miniature pigs are useful model animal for gene expression studies on dietary-induced hyperlipidemia, because they have similar digestive physiology to human. Two typical dietary components were used for dietary-induced hyperlipidemia miniature pig models. One is a high-fat and high-cholesterol diet (HFCD) containing 15% lard and 2% cholesterol, the other is a high-fat, high-cholesterol and high-sucrose diet (HFCSD) containing 15% lard, 2% cholesterol and 37% sucrose. Whole blood gene expression in HFCD, HFCSD and control male miniature pigs was measured at 10, 19 and 27 weeks of feeding periods.M-cM-^@M-^@White blood cell gene expression in HFCD, HFCSD and control male miniature pigs was measured at 27 weeks of feeding period.
Project description:Transcriptional profiling in peritoneal adipose tissue of 48 pigs (132 days of age) originated from two lines divergently selected for residual feed intake (RFI) : low-RFI pigs (RFIneg), high-RFI pigs (RFIpl). Both lines were offered isocaloric and isoproteic diets with contrasted energy source and nutrients: low fat, low fiber (LF) diet or a high fat, high fiber (HF)diet during 10 weeks. Effects of RFI selection, diet and interaction between diet and line were investigated.