Transcription profiling of left cardiac ventricle from rats with Aortic valve Regurgitation or sham operated rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Jacques Couet
PROVIDER: E-TABM-490 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR. Five male Wistar rats had one or two aortic valve leaflets punctured with a catheter under echocardiographic guidance in order to induce severe regurgitation (>65% of blood regurgitating during diastole from the aorta to the left ventricle). Five additional rats were sham-operated. The animals were sacrificed 9 months after the procedure and their left ventricle collected for RNA extraction and microarray analysis.
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Project description:Traumatic brain injury (TBI) causes hospitalizations and mortality worldwide with no approved neuroprotective treatments available, partly due to a poor understanding of the molecular mechanisms underlying TBI neuropathology and neuroprotection. We previously reported that the administration of low-dose methamphetamine (MA) induced significant functional/cognitive improvements following severe TBI in rats. We further demonstrated that MA mediates neuroprotection in part, via dopamine-dependent activation of the PI3K-AKT pathway. Here, we further investigated the proteomic changes within the rat cortex and hippocampus following mild TBI (TM), severe TBI (TS), or severe TBI plus MA treatment (TSm) compared to sham operated controls (n=78 in total). We quantified >7,000 unique proteins in total and identified 402 and 801 altered proteins (APs) with high confidence in cortical and hippocampal tissues, respectively. The overall profile of APs observed in TSm rats more closely resembled those seen in TM rather than TS rats. Pathway analysis suggested beneficial roles for acute signaling through IL-6, TGFβ, and IL-1β. Moreover, changes in fibrinogen levels observed in TSm rats suggested a potential role for these proteins in reducing/preventing TBI-induced coagulopathies. These data facilitate further investigations to identify specific pathways and proteins that may serve as key targets for the development of neuroprotective therapies.
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Project description:Gene expression along the crypt-villus (C-V) axis was analyzed using cryostat sectioning to isolate fractions representing the crypts (bottom) and villus tops (top). These fractions were used for analyzing gene expression in iron replete Wistar rats (++), iron deficient Wistar rats (low iron), and in iron deficient Wistar rats fed iron for 3 and 6 days (iron-fed). Differences were observed between the crypts and villus tops in the expression of genes associated with Wnt and BNP signaling, cell proliferation and apoptosis, lipid and iron transport and metabolism. Gene expression in villus crypts and tops was also compared between Wistar and Belgrade rats (bb) and Belgrade rats fed iron (iron-fed) particularly as related to iron absorption and metabolism to define the affects of the mutation in DMT1 in the Belgrade rat on the expression of genes related to iron absorption and metabolism and the response to iron feeding. Keywords: iron stress response A colony of Wistar strain rats (++) and Belgrade (bb) rats on a Wistar background maintained in our animal quarters was used for this study. Twelve one-month old ++ rats were separated into 3 groups of four rats each. Group 1 rats (samples 1-8) were fed a normal diet and served as control animals. Group 2 (samples 9-16) and Group 3 rats (samples 17-22) were fed a low iron diet and bled 2-3 ml every three days for 4 weeks and served as iron deficient rats (low-iron). Group 3 rats, of which one rat died during anesthesia while undergoing phlebotomy, were fed iron supplementation in drinking water (50 µM Ferric ammonium citrate) for the three days before sacrifice (iron-fed). Rats were fasted overnight, killed by injection of pentobarbital sodium and a 1-cm duodenal segment 1 cm distal from the pylorus was cryostat sectioned at the right angle to the crypt-villus axis and the sections representing the top one-third of villus (top) and the bottom one-third of the villus were pooled for RNA isolation. For the study of Belgrade rats, eleven bb rats were divided into 3 groups with the 4 rats in Group 1 (samples 23-30) maintained on a normal diet, the 4 rats in Group 2 (samples 31-38) fed iron for 3 days prior to sacrifice, and the 3 rats in Group 3 (samples 39-44) fed iron for 6 days prior to sacrifice. All procedures for the bb rats were the same as described above for the ++ rats. An additional ++ rat (samples 45-46) was similarly analyzed in a separate experiment.
2010-05-27 | E-GEOD-7970 | biostudies-arrayexpress
Project description:Early postnatal life is considered as a critical time window for determination of long-term metabolic states and organ functions. Extrauterine growth restriction (EUGR) causes the development of adult onset chronic diseases, including pulmonary arterial hypertension (PAH). However, the effects of nutritional disadvantages during early postnatal period on pulmonary vascular consequences in later life are not fully understood. Our study was designed to test whether epigentic dysregulation mediates the cellular memory of this early postnatal event. To test this hypothesis, we isolated pulmonary vascular endothelial cells (PVEC) by magnetic-activated cell sorting (MACS) from EUGR and control rats. A postnatal insult, nutritional restriction-induced EUGR caused development of an increased pulmonary artery pressure at 9-week of age in male rats. MeDIP-chip (Methyl-DNA immune precipitation chip), genome-scale mapping studies to search for differentially methylated loci between control and EUGR rats revealed significant difference in cytosine methylation between EUGR and control rats. We validated candidate dysregulated loci with quantitative assays of cytosine methylation and gene expressions. EUGR changes cytosine methylation at ~500 loci in male rats at 9 weeks of age, preceding the development of PAH and these represent candidate loci for mediating the pathogenesis of pulmonary vascular disease that occurs later in life. These results demonstrate that epigenetic dysregulation is a strong mechanism for propagating the cellular memory of early postnatal events, causing changes in expression of genes and long term susceptibility to PAH, and further providing a new insight into prevention and treatment of EUGR-related PAH. MeDIP together with microarray analysis demonstrated that significant differences in cytosine methylation between EUGR and control rats. Comparison of EUGR(n=3) vs Control (n=3) male rats' pulmonary vascular endothelial cells in 9-week age old rats
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Project description:Drug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence. Male Wistar rats (4 weeks old) were acclimatized for a week to their housing conditions prior to experiments. Thereafter, they were divided into two groups: (cohort 1) 4 groups of rats (n=12 rats per group) given saline only (i.p., "drug-naive" rats); and (cohort 2): 3 groups of rats given either methamphetamine, amphetamine or methylphenidate (5 mg/kg,i.p., M-CM-"M-bM-^BM-,M-EM-^Sdrug-pretreated") for 7 days (2x daily) prior to behavioral assays. Conditioned place preference (CPP) tests were conducted a day after the final drug administration. Rats which showed CPP were evaluated for self-administration of the psychostimulants. [Cohort 1] A day after the final self-administration test, brains of 2-3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 5 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-CM-^BM-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from 2-5 animals per group. [Cohort 2] A day after the final self-administration test, brains of 3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 3 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from three animals per group.
2013-06-27 | E-GEOD-43748 | biostudies-arrayexpress
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