Expression data from Bama minipig hearts - high-fat, high-sucrose diet
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE67890 | GEO | 2015/10/31
SECONDARY ACCESSION(S): PRJNA281120
REPOSITORIES: GEO
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Project description:In order to study the heart disorder that the long term, high energy diet caused, Bama miniature pigs were fed a high-fat, high-sucrose diet for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased heart weight (1.82-fold, P<0.05) and heart volume (1.60-fold, P<0.05) compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. The control group consisted of 6 Bama pigs fed a control diet, and the HFHSD group comprised 6 pigs that were induced with a HFHS diet, which included 37% sucrose, 53% control diet and 10% pork lard. The pigs were fed twice every day and provided water ad libitum for 23 months. The pigs were fasted for 12 hours and euthanized with ketamine and xylazine. Pig hearts from the HFHSD group pigs (120, 126, 138, 140, 144, and 146) and three control group pigs (157, 159, and 161) were sampled and preserved in liquid nitrogen and then for RNA extraction and hybridization on Affymetrix microarrays.
2015-10-31 | E-GEOD-67890 | biostudies-arrayexpress
Project description:Treatment of pathological cardiac remodeling and subsequent heart failure represents an unmet clinical need. The well conserved lncRNA H19 shows as powerful therapeutic potential in the treatment of pathological cardiac hypertrophy. H19 is strongly repressed in failing hearts from mice, pigs and humans. Gene therapy using murine but also human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Using microarray , GSEA and ChIP-Seq we identified a link between H19 and NFAT signalling. H19 physically interacts with PRC2 to epigenetically induced Tescalcin repression which in turn leads to reduced NFAT expression and activity.
2020-08-01 | GSE153375 | GEO
Project description:Treatment of pathological cardiac remodeling and subsequent heart failure represents an unmet clinical need. The well conserved lncRNA H19 shows as powerful therapeutic potential in the treatment of pathological cardiac hypertrophy. H19 is strongly repressed in failing hearts from mice, pigs and humans. Gene therapy using murine but also human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Using microarray , GSEA and ChIP-Seq we identified a link between H19 and NFAT signalling. H19 physically interacts with PRC2 to epigenetically induced Tescalcin repression which in turn leads to reduced NFAT expression and activity.
2020-08-01 | GSE153344 | GEO
Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.
2011-04-29 | E-GEOD-16790 | biostudies-arrayexpress
Project description:Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. Cardiac hypertrophy manifests as an enlargement of the individual cardiomyocytes, which impairs the function of the heart. The only way to cure end-stage cardiac myopathy is by heart transplantation, a possibility limited due to lack of donor hearts. Therefore, early diagnosis of cardiac hypertrophy is needed in order to be able to initiate interventions that may prevent further progression of the disease. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization of the model using multi-omics analyses. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48 and 72 hours and their transcriptome and secreted proteome were analyzed thoroughly. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling, actin cytoskeleton signaling and PI3K/AKT signaling. Cluster analysis of the differentially expressed genes showed that there are numerous clusters of genes that are dysregulated over the time period of 8 to 72h. An integrated transcriptome-secretome analysis enabled the identification of multimodal biomarkers of high relevance for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on transcriptomic- and secreted proteomic level. The results also provide novel insight into the underlying mechanisms of cardiac hypertrophy and novel putative early cardiac hypertrophy biomarkers have been identified that will be further validated to assess their clinical relevance.
2022-02-16 | E-MTAB-11030 | biostudies-arrayexpress
Project description:Here, we performed pathological cardiac hypertrophy transcriptome analyses by using heart tissue from Sham or TAC surgery to identify the charecteric in pathological cardiac hypertrophy. In addition, through combined analysis with the aging-associated transcriptome to identify the similarity and difference between heart ageing and pathological cardiac hypertrophy.
2025-01-29 | GSE203083 | GEO
Project description:Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n=1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.
2021-12-08 | MTBLS3174 | MetaboLights
Project description:An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiac cardiomyocytes, the transcription factor Gata4 is required for agonist-induced cardiomyocyte hypertrophy. We hypothesized that in the intact organism Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed upregulation of genes associated with apoptosis and fibrosis, including members of the TGF? pathway. Our data demonstrate that Gata4 is essential for cardiac function in the postnatal heart. After pressure overload, Gata4 regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure. Experiment Overall Design: We reasoned that if Gata4 was a crucial regulator of pathways necessary for cardiac hypertrophy, then modest reductions of Gata4 activity should result in an observable cardiac phenotype. To test this hypothesis, we used gene targeted mice that express reduced levels of Gata4. We characterized these mice at baseline and after pressure Experiment Overall Design: overload.
2007-11-13 | E-GEOD-5500 | biostudies-arrayexpress
Project description:Hypertrophic cardiomyopathy (HCM) is one of the most frequent inherited heart condition and a well-established risk factor for cardiovascular mortality worldwide. Although hypertrophy is traditionally regarded as an adaptive response to increased workload caused by physiological or pathological stress, prolonged hypertrophy can lead to heart failure characterized by impaired systolic function, increased apoptosis, fibrosis, ventricular dilation, and impaired metabolic substrate flexibility. While the key regulators for cardiac hypertrophy are well studied, the role of Prdm16 in this process remains poorly understood. In the present study, we demonstrate that Prdm16 is dispensable for cardiac development. However, it is required in the adult heart to preserve mitochondrial function and inhibit hypertrophy with advanced age. Cardiac-specific deletion of Prdm16 results in cardiac hypertrophy, excessive ventricular fibrosis, mitochondrial dysfunction, and impaired metabolic flexibility, leading to heart failure. We demonstrate that Prdm16 and euchromatic histone-lysine N- methyltransferase factors (Ehmts) act together to reduce the expression of fetal genes reactivated in pathological hypertrophy by inhibiting the functions of pro- hypertrophic transcription factor Myc. Although young Prdm16 knockout mice show normal cardiac function, they are predisposed to develop heart failure in response to metabolic stress. Collectively, our results demonstrate that Prdm16 protects the heart against age-dependent cardiac hypertrophy, fibrosis, mitochondrial dysfunction, adverse metabolic remodeling, and heart failure.
2020-09-21 | GSE153988 | GEO
Project description:VEGF family members are important regulators of vascular functions. Promoting VEGFA signalling in aged mice has been shown to delay various aging phenotypes and extend the survival of aged mice. Although there is profound knowledge on functions of VEGFA, VEGFB has not been investigated in the context of cardiac aging. Our RNA data of aged mouse hearts revealed significant downregulation of Vegfb in the heart, specifically in endothelial cells and cardiomyocytes, while VEGFB expression was reduced in endothelial cells, fibroblasts and cardiomyocytes in aged human hearts. By contrast, VEGFB expression was exclusively reduced in cardiomyocytes of patients with cardiac hypertrophy. Hence, we investigated whether Vegfb gene therapy can revert age-dependent cardiac pathologies. We overexpressed Vegfb186, the soluble VEGFB isoform, via AAV9 vector transduction into 18-month-old C57Bl/6J male mice. AAV9-Vegfb treatment prevented progression age-related diastolic dysfunction and decreased cardiac fibrosis. We further found a rescue of aging-related left ventricular denervation in the hearts of AVV9-Vegfb treated old mice which was associated with an increase in heart rate variability. However, heart to body weight ratio and cardiomyocyte hypertrophy were increased in the AAV9-Vegfb treated mouse hearts, without alteration of cardiac systolic or diastolic function. Histological and transcriptomic analyses revealed that VEGFB186 induces compensatory cardiac hypertrophy which was accompanied by a rescued length-width-ratio, reduced fibrosis and the absence of cardiac inflammation. Cardiac single-nuclei RNA sequencing further suggested that AAV9-Vegfb treatment affects cardiac hypertrophy putatively via STAT3 which was validated in vitro. In conclusion, our data reveals that Vegfb overexpression partially reverses pathological alterations in the aging heart. Despite the overall improvement of the age-related cardiac phenotype, the AAV9-Vegfb-mediated induced cardiac hypertrophy which might reflect protective hypertrophy.
2024-11-30 | E-MTAB-14595 | biostudies-arrayexpress