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Temporal changes of carotid endothelial transcriptome in hyperlipidemic pigs

ABSTRACT: Temporal changes of carotid endothelial transcriptome in hyperlipidemic pigs

PROVIDER: PRJEB10114 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR977006_1.fastq.gz	Fastqsanger.gz
	ERR977006_2.fastq.gz	Fastqsanger.gz
	ERR977007_1.fastq.gz	Fastqsanger.gz
	ERR977007_2.fastq.gz	Fastqsanger.gz
	ERR977008_1.fastq.gz	Fastqsanger.gz

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Temporal adaptation of carotid endothelial transcriptome in hyperlipidemic pigs

Project description:Temporal adaptation of carotid endothelial transcriptome in hyperlipidemic pigs

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Temporal adaptation of carotid endothelial transcriptome in hyperlipidemic pigs

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, 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.

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Temporal changes of carotid endothelial transcriptome in hyperlipidemic pigs

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.

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Project description:Recently, we showed that disturbed ﬂow caused by a partial ligation ofmouse carotid artery rapidly induces atherosclerosis. Analysis of mechanosenstive microRNA in the mouse carotid endothelium. In this study, we examined the microRNAs that respond differentially to blood flow pattern in the mouse carotid endothelium. We surgically induced disturbed blood flow in the left common carotid cartery (LCA) using partial carotid ligation surgery while the right carotid artery was left undisturbed. The hypothesis tested here is that turbulent or disturbed blood flow across the left carotid artery endothelium will affect endothelial genes and microRNAS. Identifying flow-sensitive microRNAs will provide important information about how endothelium responds to d-flow and regulates endothelial function and progression of atherosclerosis. Deter- mining the functional importance of these novel mechanosensitive microRNAS may provide important insights into understanding vascular biology and atherosclerosis. We used 6- to 8-week-old male C57Bl/6 mice (The Jackson Laboratory) according to the approved Institutional Animal Care and Use Committee protocol by Emory University. Mice were subjected to partial carotid ligation surgery under anesthesia. Brieﬂy, 3 of 4 caudal branches of LCA (left external carotid, internal carotid, and occipital artery) were ligated with 6-0 silk suture, although the superior thyroid artery was left intact. Development of low and oscillatory blood flow in the Left Carotid Artery of each mouse was determined by ultrasound measurements.

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