The calcineurin splicing variant CnAb1 reduces pressure overload-induced cardiac hypertrophy by promoting mitohormesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79536 | GEO | 2019/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Aortic banding is an excellent model system to evaluate the process of development of left ventricular hypertrophy in response to hemodynamic stress. The Affymetrix GeneChip MgU74Av1 was used to analyze expression profiles of mice at different time points after surgical intervention for pressure-overload induced hypertrophy. More information about this model may be obtained at http://cardiogenomics.med.harvard.edu/groups/proj1/pages/band_home.html Keywords = Pressure overload, cardiac hypertrophy Keywords: time-course
2002-07-30 | GSE76 | GEO
Project description:We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy. To determine the role of CHF1/Hey2 in pressure overload hypertrophy, we performed ascending aortic banding on wild type and transgenic mice overexpressing CHF1/Hey2 in the myocardium. We found that both wild type and transgenic mice developed increased ventricular weight to body weight ratios one week after aortic banding. Wild type mice also developed decreased fractional shortening after one week when compared to preoperative echocardiograms and sham operated controls. Transgenic mice, in comparison, demonstrated preserved fractional shortening. Histological examination of explanted heart tissue demonstrated extensive fibrosis in wild type hearts, but minimal fibrosis in transgenic hearts. TUNEL staining demonstrated increased apoptosis in the wild type hearts but not in the transgenic hearts. Exposure of cultured neonatal myocytes from wild type and transgenic animals to hydrogen peroxide, a potent inducer of apoptosis, demonstrated increased apoptosis in the wild type cells. Gene Set Analysis of microarray data from wild type and transgenic hearts one week after banding revealed suppression and activation of multiple pathways involving apoptosis, cell signaling and biosynthesis. These findings demonstrate that CHF1/Hey2 promotes physiological over pathological hypertrophy in pressure overload through suppression of apoptosis and global regulation of multiple transcriptional pathways.
2010-01-20 | GSE13031 | GEO
Project description:Inhibitors of DNA methyl transferase (DNMT) might be useful for treating cardiac hypertrophy by preventing de novo methylation and reduced transcription of anti-hypertrophic genes. This approach had been tested, but without a detailed phenotypic and methylation analysis. Here, we subjected rats to pressure overload and treatment with the DNMT inhibitor N-phthalyl-L-tryptophan (RG108) and analysed DNA methylation by cardiomyocyte (CM)-specific reduced representation bisulphite sequencing (RRBS).
2019-03-07 | GSE111513 | GEO
Project description:Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes.
2017-05-31 | GSE99459 | GEO
Project description:Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes.
2017-05-31 | GSE99458 | GEO
Project description:Pathological cardiac hypertrophy is a major risk factor for the development of heart failure and sudden cardiac death, yet the molecular mechanism of cardiac hypertrophy is not fully understood. Recently, we found that the expression of Lin28a, a RNA-binding protein, was significantly upregulated during the early stages of cardiac hypertrophy. Interestingly, cardiac specific conditional deletion of Lin28a blunted pressure overload-induced cardiac hypertrophic responses. Given that Lin28a can bind to diverse mRNA to regulate their abundance and/or translation, we conducted RNA-seq to profile the cardiac transcriptome alteration without Lin28a under pressure overload. It showed that metabolic pathways, including glycolysis and biosynthetic pathway, were remarkedly affected. Thus, our study identifies Lin28a as a crucial regulator of cardiac hypertrophy via its role in metabolic programming.
2019-04-30 | GSE106897 | GEO
Project description:Expression profiling of hearts from FVB males subjected to cardiac pressure overload by transverse aortic constriction (TAC). TAC performed on 8-10 weeks month old males and females. Hearts examined 30 weeks after surgery. Keywords: ordered
2005-06-29 | GSE2459 | GEO
Project description: Not available
| S-EPMC2721646 | biostudies-literature
Project description: Not available
| S-EPMC5571547 | biostudies-literature
Project description:We recently introduced a modification of the established monocrotaline (MCT) model for pulmonary hypertension (PH) and subsequent right ventricular (RV) hypertrophy, which allows for the selective induction of either a compensate or decompensated RV hypertrophic phenotype within four weeks after a single subcutaneous MCT injection. Both doses of 30 or 80 mg/kg body weight lead to an intermediate phase of compensated RV hypertrophy (day 14-19), while the former dose leads to a stable compensated phenotype (HYP) and the latter dose progresses towards decompensated ventricular hypertrophy and RV failure (CHF) around day 25-28 (Buermans et. al, Physiological Genomics 2005). This model provides the unique opportunity to characterize the development of either hypertrophic phenotype during the very early stages after imposition of RV pressure overload remodeling, well before phenotypical differences have become apparent. This experiment series describes gene expression profiles, generated by spotted oligonucleotide microarrays, to characterize and compare the expression of ~4800 genes from the RV of HYP, CHF and time matched control rats at 10, 19 and 25 days after injections. RV samples were hybridized against a common reference pool, prepared from total RNA isolated from the interventricular septum wall from animals at day 19 and 25. Keywords: dose response x time course
2006-02-01 | GSE3675 | GEO