Expression data of murine model of cardiac hypertrophy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE26671 | GEO | 2011/12/31
SECONDARY ACCESSION(S): PRJNA136419
REPOSITORIES: GEO
Similar Datasets
Project description:An initial cellular change in the pathogenesis of heart failure is cardiomyocyte hypertrophy, characterized by increased cell size, enhanced protein synthesis and reactivation of fetal genes. In addition to mechanical stresses, several neurohumoral factors have been identified as potent hypertrophic agents, including angiotensin II, endothelin, and catecholamines. We used microarrays to study the gene expression during cardiac hypertrophy. Balb/c mice (6-8w) were treated with TAC, ATII infusion, and myocardial infarction. TAC model: The transverse aorta (TAC) was constricted at the upper left sternal border by ligation with a 7-silk surgical thread and 27-gauge needle, which was removed thereafter. Sham-operated controls underwent an identical procedure without TAC. At 1 week and 1month after the procedure, LV was harvested. Ang II model.: Ang II was dissolved in 0.9% NaCl at concentrations sufficient to allow an infusion rate of 2.0 mg/kg/day, known to produce hypertension and cardiac hypertrophy. Control mice received a vehicle (saline) via an osmotic minipump. At 1 week after the procedure, LV was harvested. MI model: The proximal portion of the left coronary artery was ligated using an 8-0 nylon thread. Myocardial ischemia was confirmed by the discoloration of the heart and typical ECG changes. After 30 min occlusion, the left coronary artery was reperfused by loosening the ligature. In sham-operated mice (SHAM), the pericardium was opened, but the coronary artery was not ligated. At 1 day, 1week, and 1 month after the procedure, LV was harvested.
2011-12-31 | E-GEOD-26671 | biostudies-arrayexpress
Project description:The study aims to develop an in vitro model of cardiac hypertrophy using human induced pluripotent stem cells (hPSCs). Human stem cell based disease models are important for reducing the number of animals used in research and to get data the is more relevant to humans. We stimulated hiPSCs derived cardiomyocytes with endothelin-1 for up to 96 hours and investigated to the hypertrophic response. We measured gene expression using RNA-seq, ANP and proBNP protein, lactate and cell size.
2020-09-01 | E-MTAB-8548 | biostudies-arrayexpress
Project description:The HECT domain E3 ubiquitin protein ligase 3 (HectD3) is highly expressed in the heart, but its cardiac function is still unknown. Here, we identified SUMO2 and Stat1 as novel cardiac substrates for HectD3. SUMO2 is a potent inducer of Calcineurin-NFAT mediated cardiomyocyte hypertrophy, whereas, Stat1 is an interferon responsive transcription factor that plays crucial role in cellular immune responses. HectD3 overexpression on one hand attenuated SUMO2-Calcineurin-NFAT signaling driven cardiomyocyte hypertrophy, on the other hand, it abrogated the pro-inflammatory actions of LPS or interferon-γ in cardiomyocytes in vitro. Consistently, AAV9-mediated overexpression of HectD3 in mice in vivo not only reduced cardiac SUMO2/Stat1 levels and pathological hypertrophy but also alleviated macrophage infiltration and fibrosis induced by pressure overload. In conclusion, we describe a novel cardioprotective mechanism involving the ubiquitin ligase HectD3, which exerts anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and Stat1.
2021-09-09 | PXD020843 | Pride
Project description:Zinc dyshomeostasis has been involved in the pathogenesis of cardiac hypertrophy; however, the dynamic regulation of intracellular zinc and its downstream signaling in cardiac hypertrophy remain largely unknown. Here we screened ZIP (SLC39) family members that were responsible for zinc uptake in a phenylephrine (PE)-induced cardiomyocyte hypertrophy model. We found that Slc39a2 was the only member that was altered at mRNA level by PE treatment in neonatal rat ventricular myocytes (NRVMs), but its protein level was not affected. Zincpyr1 staining showed a significant decrease in zinc uptake after PE treatment or after Slc39a2 knockdown in NRVMs, indicating an inhibition of its transport activity during hypertrophy. Slc39a2 deficiency caused spontaneous hypertrophy in NRVMs, and further exacerbated the hypertrophic responses after PE treatment. RNA sequencing analysis confirmed a largely aggravated pro-hypertrophic transcriptome reprogramming after Slc39a2 knockdown. Interestingly, the innate immune pathways, including NOD signaling, TOLL-like receptor, NFB, and IRFs, were substantially enriched after Slc39a2 knockdown. Whereas IRF7, the most sensitive among all IRFs, did not mediate the effect of Slc39a2 in hypertrophy, pro-hypertrophy phosphorylations of NFB and STAT3 were significantly enhanced after Slc39a2 knockdown, in parallel with degradation of IkBα protein. Our data demonstrate that SLC39A2-mediated zinc homeostasis contributes to the remodeling of innate immune signaling in cardiomyocyte hypertrophy, and provide novel insights into the pathogenesis of heart failure and its treatment.
2021-11-24 | GSE175884 | GEO
Project description:We examine the role of G3bp1, a RNA binding protein and site specific endoribonuclease in gene expression in isolated neonatal cardiomyocytes. RNAseq data from cardiomyocytes were infected with adenoviruses expressing shRNA against G3bp1 (ad-siG3bp1) or Luciferase (ad-siLUC, control) showed significant decrease in transcript abudnnace of cardiac-enriched genes involved in Calcium handling, contraction, action potential and sacromere function. On the other hand increase was observed in genes that regulate Hippo, TNF and TGFb signaling. Knockdown of G3bp1 inhibited endothelin-1 induced cardiomyocyte hypertrophy.
2022-01-14 | GSE184441 | GEO
Project description:Physiological and pathological stimuli result in distinct anatomic forms of cardiac hypertrophy, but the head-to-head comparison of molecular regulation between physiological and pathological cardiac hypertrophy is less well understood, especially at the DNA methylation level. We conducted an in vitro study using human cardiomyocyte cell line AC16 exposed to angiotensin II (AngII) and insulin-like growth factor 1 (IGF-1) to mimic pathologically and physiologically hypertrophic heart models, respectively. Whole genome DNA methylation patterns were profiled by the Infinium human MethylationEPIC platform with >850K DNA methylation loci. We detected 194 loci that are significantly differentially methylated after AngII treatment (vs control) with 50.0% hypermethylated, and 206 significant loci after IGF-1 treatment (vs control) with 45.1% hypermethylated (Adjusted P < 0.05). Mapping the significant loci to genes, we identified 158 genes corresponding to AngII treatment and 175 genes to IGF-1 treatment, with 67 genes overlapping between AngII and IGF-1.
2023-10-03 | GSE241551 | GEO
Project description:Agonist-induced cardiac hypertrophy in TG1306/1R transgenic mice with cardiac angiotensin II overproduction leads to a gradual transition from a compensatory hypertrophic state to heart failure. To gain insight into the molecular mechanisms that play a role in maintaining cardiac integrity in the diseased heart, we performed a comparative study of gene expression between wild-type (WT) and transgenic (TG) hearts using microarray analysis. TG1306/1R transgenics were separated into two phenotypic groups (hypertrophic and dilated) based on morphological parameters (cardiac weight index and histology) and either a moderate (hypertrophic) or a high (dilated) upregulation of molecular markers for hypertrophy and failure, and compared to age and sex-matched wild-types. In this series, twelve 60 week old male TG1306/1R mice were separated into 3 groups: WT1-4= Four Wild-types TG1306/1R littermates genetically negative for the transgene (-/-) Hyp1-4= Four TG1306/1R mice heterozygote for the transgene (-/+) and developing a concentric hypertrophic phenotype* Dil1-4 = Four TG1306/1R mice heterozygote for the transgene (-/+) and developing a dilated cardiac phenotype* This series contains 4 biological replicates for the following triangulation: WT is compared to Hyp, WT is compared to Dil, and Hyp is compared to Dil. * For further information read: Domenighetti AA, Wang Q, Egger M, Richards SM, Pedrazzini T, Delbridge LM. Angiotensin II-mediated phenotypic cardiomyocyte remodeling leads to age-dependent cardiac dysfunction and failure. Hypertension. 2005 Aug;46(2):426-32. [PMID: 15998712]
2010-05-18 | E-GEOD-13336 | biostudies-arrayexpress
Project description:The methyltransferase-like5 (METTL5), which catalyzes m6A in 18S rRNA at position A1832, has been shown to regulate the efficient of mRNA translation in the differentiation of ES cell and the growth of cancer cells. It remains unknown that whether and how METTL5 regulates cardiac hypertrophy. In this study, we generated a mouse model (METTL5-cKO) with cardiac-specific abolishment of METTL5 in vivo. Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocyte were further confirmed with both gain- and loss-of-function approaches in primary isolated cardiomyocytes. Mechanically, METTL5 was identified to modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptome shift during cardiac hypertrophy. Therefore, our study uncover an important translational regulator of cardiac hypertrophy.
2022-02-13 | GSE186615 | GEO
Project description:Pathological cardiac hypertrophy is driven by neurohormonal activation of specific G protein-coupled receptors (GPCRs) in cardiomyocytes and is accompanied by large-scale changes in cardiomyocyte gene expression. These transcriptional changes require activity of positive transcription elongation factor b (P-TEFb), which is recruited to target genes by the bromodomain protein Brd4 or the Super Elongation Complex (SEC). Here we describe GPCR-specific regulation of these P-TEFb complexes and a novel mechanism for activating Brd4 in primary neonatal rat cardiomyocytes. The SEC was required for the hypertrophic response downstream of either the α1-adrenergic receptor (α1-AR) or the endothelin receptor (ETR). In contrast, Brd4 inhibition selectively impaired the α1-AR response. This was corroborated by the finding that activation of α1-AR, but not ETR, increased Brd4 occupancy at promoters and super enhancers of hypertrophic genes. Transcriptome analysis demonstrated that activation of both receptors initiated similar gene expression programs, but that Brd4 inhibition attenuated hypertrophic genes more robustly following α1-AR activation. Finally, we show that protein kinase A (PKA) is required for α1-AR stimulation of Brd4 chromatin occupancy. The differential role of the Brd4/P-TEFb complex in response to distinct GPCR pathways has potential clinical implications as therapies targeting this complex are currently being explored for heart failure.
2020-05-22 | GSE147402 | GEO
Project description:We show that Bmx-deficiency reduces angiotensin II -induced cardiac hypertrophy and pathological gene expression Angiotensin II or NaCl were infuced for two weeks into wild-type and Bmx-deficient mice to induce cardiac hypertrophy
2013-11-30 | E-GEOD-47420 | biostudies-arrayexpress