Assessment of miRNA expression levels in an HCM mouse model containing R403Q mutation in Myh6 gene
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE234772 | GEO | 2024/01/03
REPOSITORIES: GEO
Similar Datasets
Project description:We compared the expression levels of miRNAs in left ventricular heart tissue from HCM vs WT mice, using gene expression profiling data obtained from RNA-seq.
2024-01-03 | GSE234773 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-03 | GSE234775 | GEO
Project description:The most common form of genetic heart disease is hypertrophic cardiomyopathy (HCM), which is caused by mutations in cardiac sarcomeric genes and leads to abnormal heart muscle thickening. Complications of HCM include heart failure, arrhythmia, and sudden cardiac death. The dominant-negative c.1208 G>A (p.R403Q) mutation in b-myosin (MYH7) is a common and well-studied mutation that leads to increased cardiac contractility and HCM onset. Here we identify an adenine base editor (ABE) and single-guide RNA system that can efficiently correct this human pathogenic mutation with minimal off-target and bystander editing. We show that delivery of base editing components rescues pathological manifestations of HCM in iPSC-cardiomyocytes derived from HCM patients and in a humanized mouse model of HCM. Our findings demonstrate the use of base editing to treat inherited cardiac diseases and prompt the further development of ABE-based therapies to correct a variety of monogenic mutations causing cardiac disease.
2022-10-25 | GSE201755 | GEO
Project description:The transcriptional expression patterns in the myocardium of HCM patients may contribute to the understanding of the mechanisms that drive and stabilize the hypertrophy.
2012-06-30 | GSE32453 | GEO
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease Blood was drawn from two groups of cats: 12 healthy cats and 11 cats suffering from hypertrophic cardiomyopathy. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 23 serum samples were analyzed and the groups were compared
2015-07-22 | E-GEOD-49427 | biostudies-arrayexpress
Project description:This study is to examine gene expression profiles in 18 HCM patients and compare them with those in 5 healthy controls. The hypothesis tested here is whether patient individual-level transcriptome data integrated with the human interactom can implicate the heterogenity of HCM phenotypes.In this study, we also analyze DNA whole-exome sequencing (WES) data from 18 patients.
2021-01-09 | GSE160997 | GEO
Project description:Heart disease remains the number one killer of women in the US. Nonetheless, studies in women and female animal models continue to be underrepresented in cardiac research. Hypertrophic cardiomyopathy (HCM), the most commonly inherited cardiac disorder, has been tied to sarcomeric protein variants. Among the susceptible genes, TNNC1—encoding cardiac troponin C (cTnC)—has contributed to a substantial HCM phenotype in mice. In this study we sought to characterize the sexual dimorphism observed within cardiac physiology and transcriptomics of adult male and female mice bearing the HCM-associated cTnC-A8V point mutation. The HCM mice showed a significant decrease in stroke volume, left ventricular diameter, volume, and relative wall thickness. Importantly, isovolumetric contraction time was significantly higher for female HCM mice. RNA sequencing revealed several altered canonical pathways within the HCM mice vs WT groups including an increase in EIF2 signaling, ILK signaling, actin nucleation by ARP-WASP complex, regulation of actin-based motility by Rho, VDR/RXR activation, and glutathione redox reactions pathways. In contrast, Valine Degradation, TCA Cycle II, Methionine Degradation, and Inositol Phosphate Compound pathways were notably down regulated in HCM mice. HCM male vs. female mice followed similar trends of the canonical pathways altered between the HCM and WT. Interestingly, seven of the genes that were differentially expressed in both the WT and HCM male vs female comparisons changed directions in fold change between the sexes. These data suggest a sexually-dimorphic HCM phenotype and identify several key pathways and genes that could be critical to sex differences seen in disease manifestation.
2020-01-23 | GSE144098 | GEO
Project description:A 25-base pair deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-CΔC10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting approximately 100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-CΔC10mut in vivo are unknown. To determine whether expression of cMyBP-CΔC10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-CΔC10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-CΔC10mut. Also RNA Sequencing revealed that genes related to muscle contraction and proteosome biological process are dysregulated. Similarly,to determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C(t/t) mouse model of DCM at 3months of age.RNA-seq analysis revealed the upregulation of inflammatory pathways in the DCM hearts.
2024-03-22 | GSE262253 | GEO
Project description:A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet. To gain mechanistic insights into disease pathogenesis, we used Affymetrix microarrays to profile gene expression in left ventricular tissue from 2 month old HCM male and female mice as well as wild-type littermate controls. These mice were fed a phytoestrogen (genistein + daidzein)-supplemented casein-based diet. We identified a number of molecular pathways that could explain both the male and female phenotypes. Hearts from male and female wild-type or HCM C57BL/6 mice fed a phytoestrogen-supplemented (genistein and daidzein mix) casein-based diet were excised at 2 months of age. Total RNA was extracted from left ventricles. Biotin-labeled amplified RNA was hybridized to Affymetrix Mouse Genome 430 2.0 microarrays.
2011-06-02 | E-GEOD-29648 | biostudies-arrayexpress