Transcription profiling of rat heart at several time points after either a myocardial infraction or sham operation
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
DISEASE(S): sham surgery
SUBMITTER: Vidar Beisvag
PROVIDER: E-TABM-165 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Seventy two rats were randomized to twelve independent groups of rats (n = 6 in all groups) where half of the rats were chosen for training (treadmill exercise training 1.5 hour 5 days a week, in 1, 4, 24, 48 days and for 4 and 8 weeks) or sedentary (no training) as described in detail by Wisloff et al. (Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1301-10.) or Kemi et al.(Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation. 2004 Jun 15;109(23):2897-904. Epub 2004 Jun 1.). The rats were scarified one hour after training (1, 4, 24 and 48 days) or 24 hours after training (4 and 8 weeks). Biopsies form left ventricle was taken form all rats and stored on -80°C for preparation of RNA. The same procedures were performed for the control/sedentary rats which were sacrificed at the same time as the exercised rats.
2006-11-10 | E-TABM-166 | biostudies-arrayexpress
Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1?, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. . Male 12 wk-old C57Bl/6 mice were obtained from Charles River (Montreal, PQ, Canada) and maintained for at least 2 weeks before experimentation. Animals were randomly assigned to AL, CR and Lira groups with no initial differences in body weights. AL group mice were allowed ad libitum diet. Lira group mice were injected with Liraglutide (Glucagon-like peptide-1 agonist) at a dose of 200 µg/Kg i.p., twice daily for 7 days which is a mild weight-loss inducing dose and had access to ad libitum food and water. CR group mice were put on a Caloric restriction diet (30% less than normal ad libitum caloric intake) for 7 days to induce weight loss comparable to Lira group mice. Mice for CR and AL were individually caged and their food intake was measured everyday between 10-11 am for 1 week to calculate the average daily food intake. CR mice were fed 30% less than the calculated mean daily AL food consumption. CR cages were inspected daily for any remaining food, and transferred to a new cage every day. For CR group, pre-weighed mouse chow pellets were placed in cages between 10-11 am every day. Body weights were recorded between 10-11 am before and after the 7 day study period. For pre-ischemic assessments, animals (n=5/group/assessment) were sacrificed on day-8 (pre-MI), hearts were immediately extracted, washed in sterile phosphate-buffered saline (PBS), with LV free walls dissected, snap frozen in liquid nitrogen and stored at -80o C.
2015-05-08 | E-GEOD-68646 | biostudies-arrayexpress
Project description:Changes in gene expression contribute to the pathogenesis of heart failure. The sequence, expression level, and structure of the human cardiac transcriptome are incompletely described, as are their changes in heart disease. High throughput transcriptome sequencing (RNA-seq) is a quantitative and unbiased approach to measure transcript level and to identify novel transcribed elements or transcript splicing. Here we acquired 975.2 x 106 mapped RNA-seq reads in 15 control and 15 ischemic cardiomyopathy (ICM) hearts, obtained at the time of heart transplantation. We identified over 1000 differentially expressed transcripts, and thousands of novel transcribed elements, some of which were differentially expressed in between control and ICM groups. We found that transcript processing of several cardiac genes was deranged in ICM. For instance, the ratio between specific MYH6 exons was significantly changed in ICM compared to controls, while this type of inter-exon variation was not observed for the adjoining gene MYH7. This RNA-seq study of the human heart failure transcriptome revealed the diversity of transcripts expressed in the human heart and their complex patterns of expression in the diseased heart. Transcriptome profiling (RNA-seq) of 15 control and 15 ischemic cardiomyopathy (ICM) hearts using Illumina GAII and SOLiD
2013-12-19 | E-GEOD-48166 | biostudies-arrayexpress
Project description:Kidney samples from three Dahl Salt-sensitive S rats were compared with kidney samples from three S.R(9)x3A congenic rats.
2007-09-13 | E-GEOD-1775 | biostudies-arrayexpress
Project description:Fasting is a common dietary intervention known for its protective effects against metabolic and cardiovascular diseases. While its effects are mostly systemic, understanding tissue-specific changes in the heart is crucial for the identification of the mechanisms underlying fasting-induced cardioprotection. In this study, we performed a proteomic analysis to elucidate the proteome of the fasting heart. Our investigation identified a total of 4,652 proteins, with 127 exhibiting down-regulation and 118 showing up-regulation after fasting. Annotation analysis highlighted significant changes in processes such as lipid metabolism, the peroxisome pathway, and reactive oxygen species metabolism. Notably, the HIF-1 signaling pathway emerged as one of the focal points, with five affected proteins identified. Further experiments demonstrated down-regulation of HIF-1α at both transcript and protein levels. Intriguingly, while gene expression of Egln3 decreased, its protein product PHD3 remained unaffected by fasting. These findings underscore the regulation of the well-established cardioprotective HIF-1 signaling within the heart during 3-day fasting.
2024-10-08 | PXD050458 | Pride
Project description:Twenty-three AMI patients and 23 non-AMI healthy controls were included in this pilot study. Tissue samples were cut at 10 μm from formalin fixed paraffin-embedded tissue blocks using a microtome. Six to eight 10-μm sections were used for the isolation procedure. Total RNA isolation was performed using a miRNeasy FFPE kit (Qiagen) according to the manufacturer’s protocol. RNA concentration and purity was determined and before gene expression profiling (Affymetrix Human Exon 1.0ST Array). The microarray labeling, hybridization and processing was performed according to the manufacturer’s protocol at the Microarray Core Facility of Chinese National Human Genome Center, Shanghai, China. The raw data of microarray were quantile-normalized over all samples, summarized with the robust multi-array average (RMA) algorithm and log2 transformed with a median polish for ~22,000 transcript clusters (gene-level). Significance Analysis of Microarrays (SAM) was used to identify differential genes between AMI patients and non-AMI controls. Please note that the data files in this experiment have been previously submittted to NCBI Gene Expression Omnibus under accession numbers GSE38958 and GSE49081 (imported as E-GEOD-38958 and E-GEOD-49081 respectively in ArrayExpress ).
2016-05-11 | E-MTAB-3573 | biostudies-arrayexpress
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Designed as a 1-color experiments, samples from anterior and lateral left ventricular myocardium from non-failing, DHF and CRT animals were labeled with Cy3 and hybridized onto Agilent 44K long oligonucleotide arrays.
2010-05-16 | E-GEOD-14327 | biostudies-arrayexpress
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Complementary study to GSE14327. While GSE14327 was designed as a 1-color microarray experiment, this series was carried out following a 2-color design (anterior and lateral LV wall labeled with Cy3 and Cy5, respectively, including dye swaps).
2010-05-16 | E-GEOD-14338 | biostudies-arrayexpress
Project description:This project analyzes genome-wide cardiac DNA methylation in patients with idopathic DCM and control individuals Given are datafiles from n = 8 controls (patients after Htx) and n = 9 patients with idopathic DCM. The datasets have been normalized together with other beadchip files not subject to this study. Methylation profiles were generated from human left ventricular myocardium DNA.
2012-12-18 | E-GEOD-42510 | biostudies-arrayexpress
Project description:Careful removal of unwanted proteins is necessary for cell survival. The primary constitutive intracellular protease is the 26S proteasome complex, very often found in equilibrium with its catalytic core particle – the 20S subcomplex. Protein degradation by the former is tightly regulated due to prior selection of substrates by ubiquitination, whereas the latter is most likely confined to substrates with an inherent unstructured stretch. Understanding the interplay between 26S and 20S proteasomes is challenging due to their common catalytic sites. By using MS analyses, we define the 20S and 26S substrate preferences, and ascribe a unique property to 20S in degrading ubiquitin. High-end mass-spectroscopy of intracellular peptidome defines signature activities of 20S and finds their contribution to proteostasis under severe hypoxia and in human failing heart.
2021-11-02 | PXD018722 | Pride