Cardiac Resynchronization Therapy Corrects Dyssynchrony-induced Regional Gene Expression Changes on a Genomic Level
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris
SUBMITTER: Andreas Barth
PROVIDER: E-GEOD-14661 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:Analysis of changes of gene expression profiles in the left ventricle (LV) during the progression of heart failure (HF) in the canine tachypacing induced HF model. Gene expression profiling was performed on samples collected at different time points representing various stages of LV dysfunction, i.e. tachypaced for 3 days (Day-3), 1 week (Week-1), 2 weeks (Week-2), 3-4 weeks (End stage), and unpaced controls (Day-0). Results provide insights into molecular mechanisms of heart failure progression. Keywords: time course This work aims to study changes of gene expression profiles in the left ventricle (LV) during the progression of heart failure (HF) in the canine tachypacing induced HF model. LV transmural tissue sections were collected at different time points after initiating rapid pacing representing various stages of LV dysfunction, i.e. tachypaced for 3 days (Day-3), 1 week (Week-1), 2 weeks (Week-2), 3-4 weeks (End stage), and unpaced controls (Day-0). As biological replicates, tissues were collected separately from 3 individual dogs at each of the time points. In total we collected 15 tissue samples for all 5 time points. Three RNA samples were independently isolated from each of the 15 tissue samples as technical replicates. The resulting 45 RNA samples were used for microarray experiment. Affymetrix gene expression profiles of the 45 RNA samples were used for all data analysis in this study.
2010-05-19 | E-GEOD-9794 | biostudies-arrayexpress
Project description:T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRVβ+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRVβ repertoire in 70% of patients with Waldenstromâs Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRVβ expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRVβ expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRVβ+ restricted CTLs were confirmed by TCRVβ CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRVβ+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor. We used microarrays to detail the global programme of gene expression underlying T cell clonal expansion and identified distinct classes of up-regulated genes during this process. Experiment Overall Design: In this study we have sought T cell clones in the blood of patients with WM and related their presence with nucleoside analog therapy and transformation. We have also sorted CD3+CD4-TCRVβ+CD57+ from CD3+CD4-TCRVβ+CD57- cells and confirmed clonality by TCRVβ CDR3 size determination and sequencing and used carboxy-fluorescein diacetate succinmidyl ester (CFSE) tracking to monitor proliferation of CD3+CD4-TCRVβ+CD57+ clones. Finally we have performed microarray analysis to search for significant differentially expressed genes and pathways in the clonally expanded CD3+CD8+TCRVβ+CD57+ cells, focusing on cytotoxic pathways but also identifying other dysfunctional changes in these cells. Expression of a selection of the most differentially expressed genes detected by microarray was validated at both gene (qPCR) and protein level.
2009-12-14 | E-GEOD-18313 | biostudies-arrayexpress
Project description:Overexpression of VEGF (vascular endothelial growth factor) in the germinal matrix of the brain causes GMH-IVH-like anomalies (Germinal matrix hemorrhage [GMH]; intraventricular hemorrhage [IVH]). This dataset provides the list of differentially expressed genes in the brain cortices of embryos with transgene directed overexpression of VEGF. Eight samples were analyzed, including four control and four with induced over expression of VEGF. A simple unpaired T-test was used for analysis, with GeneSpring software,
2013-06-14 | E-GEOD-47903 | biostudies-arrayexpress
Project description:Infestation with white-backed planthopper (WBPH) to rice caused induced resistance to rice pathogens but brown planthopper (BPH) infestation induce weaker resistance to rice pathogens. We compared changes in gene expression in rice plants infested with WBPH and BPH to gain some insight into the WBPH-induced resistance to rice pathogens. An analysis, using microarrays, of gene expression in rice plants infested with these planthoppers revealed that WBPH infestation caused high induction of many defense-related genes including pathogenesis-related (PR) genes than BPH infestation. Furthermore, hydroperoxide lyase 2 (OsHPL2) which is an enzyme to produce C6 volatiles was induced by WBPH infestation, but not by BPH infestation. Experiment Overall Design: Agilent rice oligo microarray was used to investigate the gene expression profiling in rice plants infested with WBPH or BPH. Total RNA was extracted from pooled leaf blades infested with WBPH or BPH for 24 h and from mock-treated pooled leaf blades. Total RNA (200 ng) was labeled with Cy-3 or Cy-5 using an Agilent low RNA input linear amplification kit. Fluorescently labeled targets were hybridized to Agilent rice oligo microarrays. Hybridization and wash processes were performed according to the manufacturerâ??s instructions, and hybridized microarrays were scanned using an Agilent DNA microarray scanner. Agilent Feature Extraction software was employed for the image analysis and data extraction processes. Fold changes in expression level in each treatment were compared with those of the respective mock-treated controls. In each treatment, the experiment was performed independently three times.
2008-06-16 | E-GEOD-8811 | biostudies-arrayexpress
Project description:A total of 58 genes were up-regulated (> 1.5 fold-change) while 117 genes were down-regulated Microarray experiments were performed in duplicate as follows: MDA-MB-468 cells were transduced with lentiviral shRNA targeting endogenous p53-R273H mutant (p53si-1)or a non-targeting shRNA (NS). Total RNA from cells was extracted using Qiagen RNA isolation kit (Qiagen, Valencia, CA, USA) according to the manufacturersâ protocol. RNA purity was examined by spectrophotometric determination at 260/280 nm. The microarray hybridizations were carried out using the Affymetrix Human Gene 1.0 ST arrays.
2016-06-30 | E-GEOD-65967 | biostudies-arrayexpress
Project description:A total of 18 genes were up-regulated and 11 genes were down-regulated > 2-fold following 6-shogaol treatment Microarray experiments were performed in duplicate as follows: MCF-7 cells were treated with 10 uM of 6-shogaol or control vehicle (0.1% DMSO) for 48 h. Total RNA from cells was extracted using Qiagen RNA isolation kit (Qiagen, Valencia, CA, USA) according to the manufacturersM-bM-^@M-^Y protocol. RNA purity was examined by spectrophotometric determination at 260/280 nm. The microarray hybridizations were carried out using the Affymetrix Human Gene 1.0 ST arrays.
2012-09-01 | E-GEOD-36973 | biostudies-arrayexpress
Project description:High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations. Keywords: other. This dataset is part of the TransQST collection.
2002-12-06 | E-GEOD-96 | biostudies-arrayexpress
Project description:Identification of the difference in transcriptome between wild-type and SEC66 deletion mutant cells poly-A stranded RNAseq of three isolates of wild-type and three isolates of sec66â?? cells
2016-01-08 | E-GEOD-73681 | biostudies-arrayexpress