The proteomic profiling outcomes of cardiac tissues from control subjects and patients with diagnosed myocardial hypertrophy were comprehensively compared and interpreted.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Haijian Sun
PROVIDER: PXD064866 | iProX | Wed Jun 11 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Background: Although myocardial hypertrophy is an essential component of heart’s response to many forms of stress, prolonger excessive hypertrophy contributes importantly to the pathogenesis of heart disease. The pimobendan is a drug that both inhibits phosphodiesterase 3 (PDE3) and acts as a calcium sensitizer, which has been used to treat heart failure. The effects of pimobendan on myocardial hypertrophy is controversial. Objective: This study aims to evaluate the therapeutic effect of pimobendan on myocardial hypertrophy. Methods: Mice were treated with low oral doses of pimobendan (1mg/kg/d) for 4 weeks after transaortic constriction. Heart structure and function was assessed using ultrasound, hemodynamic measurements and histology combined with biochemical assessments of myocardial hypertrophy. We also examined the effects of pimobendan (100 µM) on hypertrophy in cultured neonatal rat cardiomyocytes (NRCMs) induced by 50 µM phenylephrine (PE). Results: The doses pimobendan used in our studies had no effect on baseline contractility. Nevertheless, pimobendan administration of mice subjected to TAC decreased heart weights (normalized to either tibia length or body weight) ventricular wall thickness, cardiomyocyte sizes, myocardial fibrosis and the levels of a number of key myocardial hypertrophy markers (WHICH ONES). In cultured neonatal cardiomyocytes, pimobendan attenuated the PE-induced hypertrophy. In both hypertrophy models pimobendan reduced the phosphorylation levels of several essential proteins in the MAPK pathway, PI3K-AKT pathway, and calcineurin signaling pathway. Conclusion: Low pimobendan may attenuate myocardial hypertrophy. Although the underlying mechanisms remain to be elucidated, the MAPK pathway is likely to play a role.
2023-07-01 | GSE182501 | 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:SIRT5 is one of the seven members of the NAD+-dependent sirtuin family of protein deacylase that is mainly present in mitochondria and regulates metabolism. In heart, SIRT5 is highly expressed and responsible for succinylation on metabolic enzymes. Although the role of SIRT5 in maintaining cardiac homeostasis under physiological stress and few potential substrates of SIRT5 have been preliminarily revealed, the regulatory network and key cellular signaling pathways involving SIRT5 in myocardial hypertrophy remain largely unknown. Here, we used an established murine model of pressure overload-induced myocardial hypertrophy caused by transverse aortic constriction (TAC) to outline the network and pathway involving SIRT5 in cardiac stress responses. Remarkably, SIRT5 KO mice had enhanced myocardial hypertrophy after TAC surgery compared with wild-type mice.
2024-10-05 | GSE186985 | GEO
Project description:To explore the pathogenesis of myocardial hypertrophy, Proteomic Analysis was performed to identify the differentially expressed proteins in the human myocardial tissues of non-hypertrophic control and myocardial hypertrophy patients. We used echocardiography to detect the thickness of the ventricular septum in patients undergoing heart valve replacement surgery .The thickness of the ventricular septum over 11mm is defined as myocardial hypertrophy of patients, those less than or equal to 11mm were considered as non-hypertrophic controls. We collected a total of 6 cases of non-hypertrophic controls and 6 cases of myocardial hypertrophy patients' myocardial tissues, and Proteomic Analysis was performed by mass spectrometry.
2021-06-14 | PXD023778 | Pride
Project description:Myocardial hypertrophy develops when the heart is subjected to biomechanical stress, neurohormonal or hemodynamic stimuli. Isoprenaline-induced myocardial hypertrophy in mice exhibited abnormally elevated steroid receptor RNA activator (SRA) level in hypertrophic myocardium, suggesting SRA’s potential functions in hypertrophic pathogenesis. SRA knockout or cardiac-specific knockdown attenuated cardiac remodeling without impairing baseline cardiac function. RNA sequencing and mechanistic studies identified SRA as a transcriptional coactivator that enhances GR-mediated upregulation of HSP70, which in turn activates pro-hypertrophic Akt signaling. Adenoviral SRA overexpression in H9C2 cardiomyocytes amplified isoprenaline-triggered hypertrophic gene expression via this GR-HSP70-Akt axis. Those findings establish SRA as a stress-responsive regulator of maladaptive cardiac growth and propose SRA inhibition as a targeted therapeutic strategy for hypertrophy-related cardiomyopathy. This work bridges noncoding RNA biology with metabolic signaling in heart disease, offering both mechanistic insights and translational potential.
2025-06-30 | GSE300259 | GEO
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:tRNA-derived fragments (tRFs) have served as new class of non-coding RNA and played important role in regulating cellular RNA processing and protein translation, which was also proved have function on the intergenerational effects of paternal disease. However, there was no study reported the influence of tRFs on myocardial hypertrophy. In the current study, we explore the hypothesis that tRFs in response to myocardial hypertrophy and contribute to intergenerational inheritance.We used isoproterenol induced myocardial hypertrophy rat model. Small RNA (< 40 nt) tanscriptome sequencing was used to select differential expressed tRFs. We over-expressed the highest foldchange tRFs on H9c2 cell to check its function in enlarging cardiocytes surface area. We also compared the tRFs expression pattern in F0 sperm and F1 offspring heart between myocardial hypertrophy (Hyp) and control group (Con), as well as evaluated the phynotype of myocardial hypertrophy in F1 offspring. ISO successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed tRFs were extremely enriched (84%) in Hyp heart. Overexpression tRFs1 and tRFs2 would both enlarge the surface area of cardiac cell and increase hypertrophic markers (ANF, BNP, and β-MHC) expression. tRFs1, tRFs2, tRFs3 and tRFs4 were also significantly high expressed in Hyp F0 sperm and in Hyp F1 offspring heart, but no function of tRFs7, tRFs9 and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had high expression levels of β-MHC and ANP genes, and increased fibrosis levles and apoptotic cell in heart.We demonstrate that tRFs are involved in regulating the response of myocardial hypertrophy, it might serve as novel epigenetic factor and contribute to intergenerational inheritance of cardiac hypertrophy.
2017-11-04 | GSE106511 | 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. Abdominal aorta was ligated in Wistar rats. Heart was excised 1 day, 6 days and 42 days after operation. Aorta ligated animals was compared to sham operated animals. N=6 in each time group, except aorta ligated after six days where n=5.
2010-05-27 | E-GEOD-21600 | 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
Project description:In myocardial disease, elevated expression and activity of Na+/H+ exchanger isoform 1 (NHE1) is detrimental. To better understand the involvement of NHE1, transgenic mice with elevated heart-specific NHE1 expression were studied. N-line mice expressed wild-type NHE1 and K-line mice expressed activated NHE1. Cardiac morphology, interstitial fibrosis and cardiac function were examined by histological staining and echocardiography. Differences in gene expression between the N- or K-line and non-transgenic littermates were probed using genechips. We found that NHE1 K-line hearts (but not N-line) developed hypertrophy, including elevated heart weight to body weight and increased cross sectional area of the cardiomyocytes, interstitial fibrosis, as well as depressed cardiac function. N-line transgenic hearts had modest changes in gene expression (50 up-regulations and 99 down-regulations, P<0.05), whereas K-line hearts had a very strong transcriptional response (640 up-regulations and 677 down-regulations, P<0.05). In addition, the magnitude of expression alterations was much higher in K-line than in N-line transgenic mice. The most significant changes in gene expression were involved in cardiac hypertrophy, cardiac necrosis/cell death and cardiac infarction. Secreted phosphoprotein 1 signaling pathways were up-regulated while peroxisome proliferative activated receptor gamma signaling was down-regulated in K-line mice. Our study shows that expression of activated NHE1 elicits specific pathways of gene activation in the myocardium that lead to cardiac hypertrophy, cell death and infarction.
2010-05-17 | GSE19819 | GEO