Next Generation Sequencing Facilitates Quantitative Analysis of Hypertrophic Cardiomyopathy/Healthy control Left Ventricular Transcriptomes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA789827 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In the present study, we performed the whole transcriptome resequencing in left ventricular samples from HCM patients and healthy controls. Quantitative real-time PCR (qRT-PCR) was used to validate circRNA expression. By analysing the differentially expressed circRNAs and mRNAs, we constructed the ceRNA networks based on ceRNA theory. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed of target mRNAs of differentially expressed circRNA.
2025-07-02 | GSE191120 | GEO
Project description:BACKGROUND: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies, but can result in cardiac failure if left untreated. We hypothesized that the tail-anchored protein Dysferlin with multiple Ca2+-binding C2-domains is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes, and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy. OBJECTIVE: To reveal the impact of the membrane fusion and repair protein Dysferlin on TAT network stabilization and proliferation necessary for the hypertrophic growth of cardiomyocytes. METHODS AND RESULTS: Super-resolution light and electron microscopy of mouse cardiomyocytes identified a specific localization of Dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum (SR), a.k.a. junctional complexes for Ca2+-induced Ca2+ release. Mass spectrometry was used to characterize the cardiac Dysferlin interactome, thereby identifying a novel protein interaction with the membrane-tethering SR protein Juncophilin-2, a known interactor of L-type Ca2+ channels and Ryanodine Receptor Ca2+ release channels in junctional complexes. While the Dysferlin knockout caused a mild progressive phenotype of dilated cardiomyopathy in the mouse heart, global proteome analysis revealed changes preceding systolic failure. Following transverse aortic constriction (TAC), Dysferlin protein expression was significantly increased in hypertrophied wild-type myocardium, while Dysferlin knockout animals presented markedly reduced left-ventricular hypertrophy. Live-cell membrane imaging demonstrated a profound reorganization of the TAT network in wild-type left-ventricular myocytes post-TAC with robust proliferation of axial tubules, which critically depended on the increased expression of Dysferlin within newly-emerging tubule components. CONCLUSIONS: Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-SR junctional complexes for regulated excitation-contraction coupling, and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure-overload.
2024-07-15 | PXD053051 | Pride
Project description:Pathogenic variants in MYBPC3 (myosin-binding protein C3) are the leading cause of genetic hypertrophic cardiomyopathy (HCM). Currently, there is no specific and effective treatment for this disease. Base editing is an emerging modality for treating monogenic diseases; however, its effect on MYBPC3 cardiomyopathy remains unexplored. Mybpc3-R946X/R946X mice developed early-onset left ventricular hypertrophy, systolic dysfunction, ventricular dilatation, and arrythmias. SpRY-ABEmax inefficiently corrected the Mybpc3-R946X mutation. In contrast, SpRY-ABE8e increased the efficiency by 3.6-fold and retained low level off-target editing. In vivo administration of SpRY-ABE8e efficiently corrected Mybpc3-R946X mutation in cardiomyocytes and prevented heart function decline, hypertrophic cardiomyopathy, and ventricular dysfunction. The therapeutic efficacy of SpRY-ABE8e-mediated gene correction surmounted AAV-mediated Mybpc3 gene replacement.Our study unveiled the immense potential of base editing to treat fatal inherited cardiomyopathies and opened a new avenue for the therapeutic managements of inherited cardiac diseases.
2024-04-04 | GSE239872 | GEO
Project description:Left ventricular hypertrophy, myocardial disarray and interstitital fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in plasma of HCM patients. miR-4454 is suggested as a potential biomarker for fibrosis in these patients.
2021-11-20 | GSE188324 | GEO
Project description:Strand-specific nuclear RNA-sequencing from left ventricular human heart tissue from control and hypertrophic individuals.
| PRJEB36807 | ENA
Project description:Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and impaired metabolic efficiency. This study investigates the therapeutic potential of the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) in ameliorating these pathological features in a mouse model carrying the myosin R403Q mutation. Methods: Male mice harboring the R403Q mutation were treated with EMPA for 16 weeks. We utilized multinuclear magnetic resonance spectroscopy (31P, 13C, 23Na MRS), alongside echocardiography, transcriptomic, proteomic, and phosphoproteomic profiling to assess metabolic, structural, and functional changes. Results: EMPA facilitated the coupling of glycolysis with glucose oxidation and normalized elevated intracellular sodium levels. Treatment resulted in a significant reduction in LVH and myocardial fibrosis as evidenced by echocardiography and histopathology. These structural improvements correlated with enhancements in mitochondrial ATP synthesis, fatty acid oxidation (FAO), and branched-chain amino acid (BCAA) catabolism. Furthermore, empagliflozin improved left ventricular diastolic function and contractile reserve, underscored by improved ATP production and reduced energy cost of contraction. Notably, these benefits were linked to downregulation of the mTOR signaling pathway and normalization of myocardial substrate metabolic fluxes. Conclusion: EMPA significantly mitigates structural and metabolic dysfunctions in a mouse model of HCM, underscoring its potential as a therapeutic agent for managing this condition. These findings suggest broader applicability of SGLT2 inhibitors in cardiovascular diseases, including those due to myocardial-specific mutations, warranting further clinical investigation.
2025-06-09 | GSE270093 | GEO
Project description:Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in α-tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLB), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; the hearts of these mice exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories show that the hearts of mice that were genetically crossed between the Tm180 and PLB KO mice rescues the hypertrophic phenotype and improves their cardiac morphology and function. We used microarrays to detail the global program of gene expression underlying cardiac remodeling and rescue of the hypertrophic cardiomyopathic phenotype and identified distinct classes of regulated genes during this process. To understand the changes in gene expression that occur over time in these animal models (Tm180, PLB KO, Tm180/PLB KO and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 months of age.
2012-12-13 | E-GEOD-42892 | biostudies-arrayexpress
Project description:The SGLT2 Inhibitor Empagliflozin Enhances Metabolic Efficiency and Ameliorates Left Ventricular Hypertrophy in Myosin R403Q Mutant Hypertrophic Cardiomyopathy Mice
| PRJNA1124979 | ENA
Project description:We wanted to see whether the set of affected genes in ischemic cardiomyopathy (ICM) is the same or different as compared to dilated cardiomyopathy (DCM). To find this out, we placed the single DCM sample on the same microarray slide with the ICM samples. Analysis of microarray data with ICM samples only showed 63 affected genes, while that carried out with 2 ICM samples PLUS one DCM sample reduced this number to just four genes. From this result we conclude that ICM and DCM affect different sets of genes in ventricular myocytes. Keywords: Expression profiling by array From the associated publication: To find out whether the splice microarray results reported in Table 3 are disease-type specific, we supplemented the same splice microarray of ICM ventricular myocytes with one additional sample prepared from left ventricle of a 41-years old dilated cardiomyopathy male donor. The top-list ANOVA gene score annotation for combined altered CE&P genes in ventricular myocytes (Table 3) was reduced from 63 to just 4 genes (FXYD1 (Gfold = +2.4), HCN2 (-1.5), GLRA1 (-1.8) and GJC1 (-2.3)).
2010-06-17 | E-GEOD-17530 | biostudies-arrayexpress
Project description:Aims: Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with progressive myocardial hypertrophy, fibrosis, ventricular dysfunction, and arrhythmias. Hypoxia together with hypoxia-inducible transcription factor-1a (HIF1A) is the central master regulators of cellular hypoxia response and associated with HCM. Yet their exact role remains to be elucidated. Therefore, the effect of a cardiomyocyte-specific Hif-1a knockout (cHif1aKO) was studied in an established α-MHC719/+ HCM mouse model that exhibits the classical features of human HCM. Results: HIF-1α protein and HIF downstream targets were upregulated in left ventricular tissue of α-MHC719/+ mice. Cardiomyocyte-specific abolishment of Hif-1a did not cause cardiac abnormalities in wild type (WT) mice and resulted in amelioration of disease phenotype in α-MHC719/+ mice, as evidenced by decreased left ventricular wall thickness, reduced myocardial fibrosis, reduced disordered SRX/DRX state and diminished ROS production. In addition, cHif1aKO induced normalization of pro-hypertrophic and pro-fibrotic left ventricular remodeling signaling evidenced on whole transcriptome and proteomics analysis in α-MHC719/+ mice. Proteomics of serum samples from patients with early onset HCM compared to age-and gender-matched healthy controls revealed significant upregulation of HIF targets IGF2, LTBP1, RECK and downregulation of WDR1. Innovation and Conclusion: Overall, these results demonstrate for the first time that HIF signaling is involved in mouse and human HCM pathogenesis. Cardiomyocyte-specific knockout of Hif-1a attenuates disease phenotype in the HCM α-MHC719/+ mouse model. Targeting HIF-1α might serve as a therapeutic option to mitigate HCM disease progression.
2025-01-22 | GSE266649 | GEO