Unknown,Transcriptomics,Genomics,Proteomics

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Differential gene expression is not correlated to age-related vascular pathology in aorta and mesenteric artery of Brown Norway and Fischer344xBrown Norway rats

ABSTRACT: Novel genetic pathways associated with successful and/or unsuccessful vascular aging Customized therapies for vascular disease will require matching the vessel type and genetic background of the patient. Our previous studies showed that progressive age-related vascular pathology is strain specific in the thoracic aorta (TA) and mesenteric arteries (MA) of the Brown Norway (BN) and the Fisher344/Brown Norway F1 hybrid (F1) rats. The purpose of this study was to identify novel genetic pathways associated with successful and/or unsuccessful vascular aging. TA and MA were collected from anesthetized 6, 15 and 24 month old age-matched F1 and BN rats for total RNA isolation. The gene microarrays were generated using the Affimetrix GeneChip Rat Expression 230A Array. Gene expression data was analyzed with the Ingenuity Pathway Analysis and proprietary software. Despite more pronounced age-related vascular pathology in the F1 strain, more genes were differentially expressed in the BN strain during aging. A sample of common key genes (KLB1, TRIO, HLA-C and PCP4) showed similar expression at 6 and 15 months and downregulation at 24 months in F1 vs. upregulation in BN rats. Among the top 50 canonical pathways there was only a 10 and 30% overlap, respectively, between the F1 and BN strains in MA and TA. Most of the overexpressed molecules associated with the same vascular-related biological functions are different between strains. The data suggest that age-related vascular pathology and decrement in function is both strain and vessel-dependent and different genetic programs could be employed to accomplish both normal and pathological physiological processes in conduit and resistance arteries. two strains: two vessel types, 3 different ages

ORGANISM(S): Rattus norvegicus

SUBMITTER: Gabriel Gruionu

PROVIDER: E-GEOD-55612 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:This study utilized a standard rat model of aging and global gene expression analyses to attempt to identify the most appropriate time points to study vascular aging and to identify molecules associated with the development of pathology. Recent studies have established that age is the major risk factor for vascular disease. Numerous changes occur in vascular structure and function during aging, and animal models, including rodents, are the primary means to determine the underlying mechanisms of age-mediated vascular pathology. This study utilized a standard rat model of aging and both morphometric and global gene expression analyses to attempt to identify the most appropriate time points to study vascular aging and to identify molecules associated with the development of pathology. Morphometric analysis of Fischer 344/Brown Norway F1 hybrid (F344xBN) rat thoracic aorta indicated, in contrast to some previous studies, that progressive increases in intimal and medial thickness, as well as smooth muscle cell-containing intimal protrusions, occurred with age. This structural vascular pathology was associated with a progressive increase in global differential gene expression. Specific molecules with altered mRNA and protein expression included the adhesion molecules ICAM-1 and VCAM-1, and the bone morphogenic proteins osteopontin and bone sialoprotein-1. Intimal-associated macrophages were detected with immunohistochemistry in paraffin sections of thoracic aorta and were found to increase significantly in number with age. Both systemic and tissue markers of oxidant stress, serum 8-isoprostane and 3-nitrotyrosine, respectively, were found to increase during aging. The results demonstrate that increased inflammation and oxidant stress occur progressively during vascular aging, and suggest therapeutic targets to limit or reverse aging-associated vascular pathology and dysfunction. Experiment Overall Design: Samples were taken from rats at 4 ages, 3mo, 6mo, 15mo and 28 mo, with 4 replicates in each age group.

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Differential gene expression is not correlated to age-related vascular pathology in aorta and mesenteric artery of Brown Norway and Fischer344xBrown Norway rats

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