Rattus norvegicus
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PROVIDER: PRJNA240218 | ENA |
REPOSITORIES: ENA
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Project description: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
2015-03-02 | E-GEOD-55612 | biostudies-arrayexpress
Project description: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.
2015-03-02 | GSE55612 | GEO
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.
2008-06-15 | E-GEOD-7281 | biostudies-arrayexpress
Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile microRNAs in thoracic descending aorta of SS and congenic rats fed NSD or HSD.
2021-03-22 | GSE149515 | GEO
Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) in thoracic descending aorta of SS and congenic rats fed NSD or HSD.
2021-03-22 | GSE149514 | GEO
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. Keywords: time course
2007-10-29 | GSE7281 | GEO
Project description:Comparison of gene expression levels in ductus arteriosus (DA) and aorta in full-term (21 days) neonates of Brown-Norway (BN) and Fischer344 (F344) rats We analyzed the fold difference between BN and F344 rats in ductus arteriosus in order to identify the down-regulated and up-regulated genes specifically in BN rat's DA. The differences in aorta was also examined for additional comparison.
2015-08-29 | GSE40534 | GEO
Project description:Background: The vascular wall of small arteries is heavily affected by high blood pressure. However, the underlying mechanisms causing vascular changes are not fully elucidated. Using a novel data-independent acquisition mass spectrometry (DIA-MS) approach, we aimed to determine the proteomic changes in small mesenteric arteries during early-onset high blood pressure in a rat model of hypertension. Methods: Snap frozen small mesenteric and renal arteries from the spontaneous hypertension rat (SHR) model and Wistar Kyoto (WKY) control rats were collected from two time points (6- and 12-weels of age) and analyzed by a label free quantitative DIA-MS workflow. Mesenteric arteries from Wister Hannover rats were included as an additional control to clarify genetic drift caused by selective inbreeding. Results: We identified a total of 3956 consistent proteins in the mesenteric artery wall and found that 286 proteins were significantly regulated in 12-weeks old SHRs compared to WKY controls. Comparing to an in silico matrisome database, we identified 38 extracellular matrix-associated proteins that could distinguish SHRs from WKY controls. Furthermore, when comparing the significantly regulated proteins identified in mesenteric and renal arteries, we identified 18 proteins, including Serpina3l, Igg-2a, ENSRNOG00000049829, Acyp2, Enpp3, Lss, Acaa1a, Basp1, an isoform of Basp1, Flot1, Flot2, Gstt1, Nit1, Ppid, Ikbkap, Poglut3, P4ha2 and Usp15, that were changed in both vascular beds. These proteins were associated with vital cellular processes, such as dyslipidemia, protease inhibition, remodeling and generation of reactive oxygen species. Majority of the identified proteins and pathways were associated with hypertension, and mapping the underlying changes help understanding the pathological processes occurring in the arterial wall during early-onset hypertension. Conclusions: Our data provides an in-depth analysis of the proteomic architecture of the mesenteric and renal artery wall from SHRs and WKY control rats. We identified 18 novel candidate proteins that highlights critical changes in small arteries of the SHR.
2022-01-06 | PXD026051 | Pride
Project description:In order to gain insight into the effects of aging on susceptibility to environmental toxins, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of male Brown Norway and F344 rats across the adult lifespan. To examine metabolic processes across lifespan after challenge with a xenobiotic compound, Brown Norway rats were exposed to 1.0 g/kg body weight toluene by oral gavage in corn oil (4ml/kg body weight) or corn oil alone. Keywords: age effect on toxin susceptibility
2008-07-30 | GSE11097 | GEO
Project description:This study used Deep RNA sequencing to define gene expression in the small resistance arteries and compare to a reference conduit artery, the aorta Methods: Deep RNA Sequencing (~90 million reads) was performed on 2 samples of adult SD rat mesenteric arteries and compared to that of 2 samples of aorta. Results: ~900 genes were identified that were expressed at least 2-fold difference between meseteric artery and aorta mRNA profiles of 2 samples of rat mesenteric artery and 2 samples of rat aorta were sequenced using Illumina HiSeq
2015-07-13 | E-GEOD-64450 | biostudies-arrayexpress