Effect of cardiac specific KO of p38 MAPKα on gene expression profile of the heart
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE86075 | GEO | 2017/11/30
SECONDARY ACCESSION(S): PRJNA340178
REPOSITORIES: GEO
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Project description:p38MAPKα KO mice develop in response to Angiotensin II treatment a dilative cardiomyopathy. Gene expression profile of KO hearts was compared to equally treated control heart under baseline conditions and after 48 hours of Angiotensin II treatment via osmotic mini pumps.
2017-11-30 | GSE86074 | GEO
Project description:Analysis of angiotensin II effect on left ventricle at gene expression level. The hypothesis tested in the present study was that angiotensin II treatment may affect gene expression in left ventricle in a strain specific manner. Results provide important information about which genes respond to angiotensin II in C57Bl/6N male mice compared to their C57Bl/6J counterparts. Total RNA obtained from isolated left ventricles from C57Bl/6J and C57Bl/6N mice subjected to 48 hours of angiotensin II infusion, via osmotic mini-pumps (500ng/kg/h) implanted sub-cutaneously, compared to sham operated controls.
2014-12-12 | E-GEOD-53269 | biostudies-arrayexpress
Project description:To analyze Gq-receptor hypertrophic transcriptional profiles, 10 to 11 week old FVB/NJ mice were dosed at 30 mg/kg/day for phenylephrine and 0.5 mg/kg/day for angiotensin II using implanted micro-osmotic pumps (Alzet, model 1002) for 72 hours. Total RNA was harvested from isolated myocytes using RNeasy Fibrous Tissue Mini Kit (Qiagen), following manufacturer’s instructions. Using total RNA as input, rRNA was removed via oligo-dT purification to enrich for mRNA, followed by random-primed reverse-transcription, second-strand cDNA synthesis, ligation of indexed adaptors for Illumina sequencing, and subsequent library creation from the resulting double-stranded DNA. 125 base pair paired end stranded RNA Sequencing was performed by the University of Minnesota Genomics Core using the Illumina HiSeq 2500 resulting in 10-20 million reads per sample.
2018-05-12 | E-MTAB-6770 | biostudies-arrayexpress
Project description:Ghsr-/- mice and WT controls (14 weeks-old, n = 3 / group) were used to analyse whole genome gene expression in the hippocampal DG. Briefly, mice were prepared with jugular vein cannulae attached to osmotic mini-pumps (Alzet model 2001) under isofluorane anesthesia. The mini-pumps delivered either vehicle or acyl-ghrelin (48μg/day; Phoenix Pharmaceuticals, USA) for 7 days. Mice were killed by cervical dislocation and whole brain was removed and immediately snap frozen on dry ice and stored at -80oC prior to T-RNA extraction for microarray analysis.
2022-11-01 | E-MTAB-3601 | biostudies-arrayexpress
Project description:Background: The insulin/IGF/relaxin family represents a group of structurally related but functionally diverse proteins. The family member Relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of Insulin-like peptide 6 (Insl6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. Methods and Results: Insl6-deficient (Insl6-KO) and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively for 2 weeks. In both models, Insl6-KO mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation hypertrophy. Cardiac dysfunction in the Insl6-KO mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis-associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests Lxr/ Rxr signaling is activated in the isoproterenol-challenged hearts treated with INSL6 protein. Conclusions: Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II- and isoproterenol-induced cardiac stress models. The administration of recombinant Insl6 protein could have utility for the treatment of heart failure and cardiac fibrosis.
2018-05-31 | GSE102612 | GEO
Project description:We characterized the metabolic and cardiac mitochondrial function in a mouse model of non-ischemic HF. Inhibition of nitric oxide synthesis and hypertension, which often present together, are two important risk factors in human non-ischemic HF. Compared with L-NAME L-NG-Nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis or Angiotensin II (AngII), a hypertensive agent treatment alone, L-NAME+AngII induced the most severe HF phenotype characterized by edema, hypertrophy, fibrosis, increased blood pressure and reduced ejection fractions. L-NAME+AngII treated mice had robust deterioration of cardiac mitochondrial function we observed. Microarray analyses revealed majority of the gene changes attributed to the combination of L-NAME+AngII. Pathway analyses indicated significant changes in metabolic pathways such as mitochondrial oxidative phosphorylation, fatty acid metabolism and tricarboxylic acid pathways etc.in L-NAME+AngII hearts. We conclude that combination of L-NAME+AngII exacerbates cardiac contractile and mitochondrial functional de-regulation compared with L-NAME and AngII alone, resulting in non-ischemic HF. This model of heart failure may be highly valuable in studying mechanisms and treatments for non-ischemic heart failure. Twelve week-old C57BL6 male mice were randomly assigned to 4 groups: 1. Control, 2. L-NAME treatment, 3. AngII treatment, 4. L-NAME+AngII treatment.L-NAME (0.3 mg/ml with 1% NaCl) was administered in drinking water. AngII (0.7 mg/kg/day) was administered via subcutaneous micro-osmotic pumps. L-NAME and AngII were administered to mice for 5 weeks and 4 weeks in combination to induce HF or alone to study the effects of the individual agents.
2016-01-19 | E-GEOD-72132 | biostudies-arrayexpress
Project description:Aims: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that constitutes several distinct phenotypes, including a common cardiometabolic phenotype with obesity and type 2 diabetes mellitus. Treatment options for HFpEF are limited, and development of novel therapeutics is hindered by the paucity of suitable preclinical HFpEF models that recapitulate the complexity of human HFpEF. Metabolic drugs, like Glucagon Like Peptide Receptor Agonist (GLP-1RA) and Sodium Glucose Transporter 2 inhibitors (SGLT2i), have emerged as promising drugs to restore metabolic perturbations and may have value in the treatment of the cardiometabolic HFpEF phenotype. We aimed to develop a multifactorial HFpEF mouse model that closely resembles the cardiometabolic HFpEF phenotype, and evaluated the GLP-1 RA liraglutide and a SGLT2i dapagliflozin. Methods&Results: Aged (18-22 months old) female C57BL/6J mice were fed a standardized chow (CTRL) or high fat diet (HFD) for 12 weeks. After 8 weeks HFD, Angiotensin-II (ANGII), was administered for 4 weeks via osmotic mini-pumps. HFD+ANGII resulted in a cardiometabolic HFpEF phenotype, including obesity, impaired glucose handling and metabolic dysregulation with inflammation. The multiple-hit resulted in typical clinical HFpEF features, including cardiac hypertrophy and fibrosis with preserved fractional shortening but with impaired myocardial deformation, atrial enlargement lung congestion, and elevated blood pressures. Treatment with liraglutide attenuated the cardiometabolic dysregulation and improved cardiac function, with reduced cardiac hypertrophy, less myocardial fibrosis, and attenuation of atrial weight, natriuretic peptide levels, and lung congestion. Dapagliflozin treatment improved glucose handling, but had mild effects on the HFpEF phenotype. Conclusions: We developed a mouse model that recapitulates the human HFpEF disease, providing a novel opportunity to study disease pathogenesis and development of enhanced therapeutic approaches. We furthermore show that attenuation of cardiometabolic dysregulation may represent a novel therapeutic target for treatment of HFpEF.
2020-09-16 | GSE153923 | GEO
Project description:To establish changes in cardiac transcription profiles brought about by heart failure we collected myocardial samples from patients undergoing cardiac transplantation whose failure arises from different etiologies (e.g. idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, alcoholic cardiomyopathy, valvular cardiomyopathy, and hypertrophic cardiomyopathy) and from "normal" organ donors whose hearts cannot be used for transplants. The transcriptional profile of the mRNA in these samples will be measured with gene array technology. Changes in transcriptional profiles can be correlated with the physiologic profile of heart-failure hearts acquired at the time of transplantation. Keywords: other
2004-03-24 | E-GEOD-1145 | biostudies-arrayexpress
Project description:To test the mechanism by which IGF1 is cardioprotective, we performed single cell RNA sequencing on myeloid cells isolated from the heart 3 days after myocardial infarction of mice with and without IGF1 treatment. Myocardial infarction was induced in C57Bl6/J mice by 45 min occlusion of the left anterior descending artery followed by 3 days of reperfusion. Animals of the IGF1 group (n=3) received 40 ng/g mature recombinant IGF1 subcutaneously as bolus at the beginning of reperfusion. In addition, IGF1 (1 µg/g/d) was administered continuously during reperfusion using micro-osmotic pumps (Alzet, 1003D) that were implanted subcutaneously. Control mice received vehicle (0.1% BSA). After 3 days hearts were digested and CD45+CD11b+ cells were isolated using FACS cell sorting. Each sample contained cells containing 1 control and 1 IGF1 treated mouse, labeled with TotalSeq hashtags. 16000 cells were used as input for the single-cell droplet libraries generation for each sample.
2023-12-31 | E-MTAB-11590 | biostudies-arrayexpress
Project description:Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFII’s effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy.
2015-07-24 | GSE63759 | GEO