RNA sequencing reveals novel LncRNAs/mRNAs network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE176244 | GEO | 2021/06/09
REPOSITORIES: GEO
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Project description:RNA sequencing reveals novel LncRNAs/mRNAs network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
| PRJNA735548 | ENA
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:Cardiac hypertrophy was induced by aortic banding (6, 12, 16, and 30 weeks), myocardial infarction (3 and 9 weeks), an av-fistula (aorta abd. to v. cava inf.. 3 and 8 weeks), or hormone infusion (two weeks either angiotensin 2 or a thyroxin analogue). Sham operated or saline infused animals served as controls. Gene expression was determined by Affymetrix RGU34A GeneChip's to identify genes with common regulation in the different models of cardiac hypertrophy. Keywords: other
2004-03-12 | GSE738 | GEO
Project description:Mutation of the PRDM16 gene causes human dilated and noncompaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN.
2023-07-21 | PXD043601 | Pride
Project description:Cardiac hypertrophy consists in the enlargement of cardiomyocytes and alteration of the extracellular matrix organization in response to physiological or pathological stress. In pathological hypertrophy ocuurs myocardial damage, loss of cardiomyocytes, fibrosis, inflammation, sarcomere disorganization and metabolic impairment, leading to cardiac dysfunction.The rodent model treated with isoproterenol induces cardiac hypertrophy due the constant activation of β-adrenergic receptors. We conducted a quantitative label-free proteomic analysis of cardiomyocytes isolated from hearts of mice treated or not with isoproterenol to better understand the molecular bases of cellular response due to isoproterenol-induced injury.
2020-05-27 | PXD013020 | Pride
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:Comparison of both LncRNAs and mRNAs expression in the border zone of the myocardial infarction rats and the sham operation rats Border zone (BZ) of the myocardial infarction is critical to patients. Current treatments of myocardial infarction are primarily aimed to save the dying myocardial cell in the border zone. During myocardial infarction, certain changes in BZ, e.g, apoptosis, fibrosis, inflammation, etc, played an important role in deciding the survival. Impairment and recovery of BZ has been linked to gene expression changes. The aim of our study was to obtain a global expression profile of lncRNAs and mRNAs of the border zone in Wistar rats myocardial infarction, and identify the changes during myocardial infarction.
2016-12-02 | GSE90745 | GEO
Project description:To further investigate the role of hyaluronan and the regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study correlation over time.
2010-05-01 | GSE21600 | GEO
Project description:Purpose: The physiological cardiac hypertrophy is an adaptive condition that does not associate with myocyte cell death while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. Alpha-2 macroglobulin (α-2M) an acute phase protein induces cardiac hypertrophy via the ERK1,2 and PI3K/Akt signaling. This study is aimed at exploring the miRNome of α-2M induced hypertrophied cardiomyocytes and to understand the role of miRNAs in determination of pathological and physiological hypertrophy. Methods: Hypertrophy was induced in H9c2 cardiomyoblasts using alpha-2 macroglobulin. The induction of hypertrophy is confirmed by microscopy and gene expression studies. Subsequently, the total RNA was isolated and small RNA sequencing was executed in Illumina HiSeq 2000. Results: Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy. Among the differentially expressed candidates, miR-99 family (miR-99a, miR-99b and miR-100) showed significant downregulation upon α-2M treatment while isoproterenol treatment (pathological hypertrophy) upregulated their expression. The binding site for Egr1 transcription factor was identified in the promoter region of miR-99 family, and interestingly all miRNAs with Egr1 binding site proven by ChIP-Seq were downregulated during physiological hypertrophy Conclusions: The results proved Egr-1 mediated regulation of miR-99 family determines the uniqueness of pathological and physiological hypertrophy. Upregulated miR-99 expression during pathological hypertrophy suggests that it can be a valuable diagnostic marker and potential therapeutic target for cardiac hypertrophy and heart failure. Small RNA profiles of control and hypertrophied cardiomyocyte H9c2 cells were generated by deep sequencing using Illumina HiSeq 2000
2015-11-01 | E-GEOD-73597 | biostudies-arrayexpress
Project description:Kinase-catalyzed phosphorylation plays crucial roles in numerous biological processes. CDC-like kinases (CLKs) are a group of evolutionarily conserved dual-specificity kinases that have been implicated in RNA splicing, glucose metabolism, diet-induced thermogenesis and so on. However, it is still largely unknown whether CLKs are involved in pathologic cardiac hypertrophy. This study aimed to investigate the role of CLKs in pathologic cardiac hypertrophy and the underlying mechanisms. Using small RNA interference, we discovered that defects in CLK4, but not CLK1, CLK2 or CLK3, were associated with the pathogenesis of pathological cardiomyocyte hypertrophy, while overexpression of CLK4 exerted resistance to isoproterenol-induced pathological cardiomyocyte hypertrophy. Moreover, the expression of CLK4 was significantly reduced in the failed myocardia of mice subjected to either transverse aortic constriction or isoproterenol infusion. Through the Cre/loxP system, we constructed cardiac-specific Clk4-knockout (Clk4-cKO) mice, which manifested pathological myocardial hypertrophy with progressive left ventricular systolic dysfunction and heart dilation. Phosphoproteomic analysis revealed significant changes in phosphorylation of sarcomere-related proteins in Clk4-cKO mice. Further experiments identified nexilin (NEXN), an F-actin binding protein, as the direct substrate of CLK4, and overexpression of a phosphorylation-mimic mutant of NEXN was sufficient to reverse the hypertrophic growth of cardiomyocytes induced by Clk4 knockdown. Importantly, restoring the phosphorylated NEXN significantly ameliorated the myocardial hypertrophy in Clk4-cKO mice. CLK4 phosphorylates NEXN to regulate the development of pathological cardiac hypertrophy. CLK4 may serve as a potential intervention target for the prevention and treatment of heart failure.
2022-07-05 | PXD029682 | Pride