Dataset Information

Cardiac ?-adrenoceptor expression is markedly depressed in Ossabaw swine model of cardiometabolic risk.

ABSTRACT: Ossabaw swine have a "thrifty genotype" and consumption of excess calories induces many classical components of the metabolic syndrome, including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and hypertension. Earlier studies indicate that the metabolic syndrome is associated with diminished cardiac function; however, to what degree this impairment is associated with alterations in myocardial ?(1)- and ?(2)-adrenoceptor (AR) expression has not been fully elucidated. Accordingly, the present study was designed to investigate the effects of the metabolic syndrome on cardiac ?(1)- and ?(2)-AR expression. Studies were conducted on left ventricular tissue samples obtained from control lean and chronically (50 weeks) high-fat-fed obese animals. Chronic feeding significantly increased fasting plasma insulin, total cholesterol, triglycerides, blood glucose, systolic and diastolic blood pressure, and heart rate. Real-time polymerase chain reaction revealed no significant alterations in cardiac ?(1)- and ?(2)-AR mRNA expression. In contrast, Western blot analysis revealed a significant decrease in ventricular ?(1)- and ?(2)-AR protein expression. This is the first report in a novel large animal model that induction of metabolic syndrome is accompanied by a significant reduction in cardiac ?(1)- and ?(2)-AR protein expression that could contribute to impaired cardiac function.

SUBMITTER: Dincer UD

PROVIDER: S-EPMC3133518 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Cardiac β-adrenoceptor expression is markedly depressed in Ossabaw swine model of cardiometabolic risk.

Dincer U Deniz UD

International journal of general medicine 20110624

Ossabaw swine have a "thrifty genotype" and consumption of excess calories induces many classical components of the metabolic syndrome, including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and hypertension. Earlier studies indicate that the metabolic syndrome is associated with diminished cardiac function; however, to what degree this impairment is associated with alterations in myocardial β(1)- and β(2)-adrenoceptor (AR) expression has not been fully ...[more]

PMID: 21760751

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Project description:We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n=5) and lean (n=6) juvenile Ossabaw pigs (age=22 weeks). Obesity was experimentally induced by feeding the animals a high-fat/high fructose corn syrup/high-cholesterol diet for 16 weeks. We found that expression of 189 vascular cell genes in the LAD and expression of 165 genes in the thoracic aorta were altered with juvenile obesity (FDRM-bM-^IM-$10%) with an overlap of only 28 genes between both arteries. Notably, a number of genes found to be markedly up-regulated in the LAD of obese pigs are implicated in atherosclerosis, including ACP5, LYZ, CXCL14, APOE, PLA2G7, LGALS3, SPP1, ITGB2, CYBB, and P2RY12. Furthermore, pathway analysis revealed the induction of pro-inflammatory and pro-oxidant pathways with obesity primarily in the LAD. Gene expression in the LAD perivascular fat was minimally altered with juvenile obesity. Together, we provide new evidence that obesity produces artery-specific changes in pre-translational regulation with a clear up-regulation of pro-atherogenic genes in the LAD. Our data may offer potential viable drug targets and mechanistic insights regarding the molecular precursors involved in the origins of over-nutrition and obesity-associated vascular disease. In particular, our results suggest that the oxLDL-LOX-1-NFM-NM-:B signaling axis may be involved in the early initiation of a juvenile obesity-induced pro-atherogenic coronary artery phenotype. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n=5) and lean (n=6) juvenile Ossabaw pigs (age= 22 weeks). All three tissue types were taken from each animal, and each was applied to one and only one array array except a single Thoracic aorta (Animal ID 63 because there were not enough arrays), so there were 32 total arrays (11 unique pigs).

Dataset Information

Cardiac ?-adrenoceptor expression is markedly depressed in Ossabaw swine model of cardiometabolic risk.

Publications

Cardiac β-adrenoceptor expression is markedly depressed in Ossabaw swine model of cardiometabolic risk.

Similar Datasets

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