Regulation of the Balance between Concentric and Eccentric Cardiac Hypertrophy by a CDC14A-KMT5A Signaling Pathway
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE318858 | GEO | 2026/02/17
REPOSITORIES: GEO
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Project description:The lysine methyltransferase KMT5A is shown to mediate the effects of CDC14A in the adult cardiomyocyte by regulating H4K20 mono-methylation, such that reduced KMT5A expression promotes a phenotype resembling Dilated Cardiomyopathy.
2026-02-18 | GSE318470 | GEO
Project description:Regulation of the Balance between Concentric and Eccentric Cardiac Hypertrophy by a CDC14A-KMT5A Signaling Pathway
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Project description:Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFII’s effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy. We utilized a previously established CAG-S-COUP-TFII allele and crossed it with the Myh6-MerCreMer (Myh6-MCM) line to overexpress COUP-TFII specifically in cardiomyocytes at two months of age by administration of tamoxifen. The experimental group has genotype of Myh6-MCM; CAG-S-COUP-TFII while the control group consists of Myh6-MCM mice (Figure 1C). Whole ventricles were harvested 16 days post induction for molecular profiling.
2015-07-24 | E-GEOD-63759 | biostudies-arrayexpress
Project description:This experiment aimed to investigate the transcriptional role of G4 resolvase Dhx36 in the adult mouse heart. We compared three pools of wild-type (WT) mouse hearts with three pools of Dhx36 conditional knockout (cKO) hearts. In the mutant mice, Dhx36 was conditionally deleted in cardiomyocytes using the Myh6-cre transgenic line. Each of the six pools was created using RNA extracted from 3-5 hearts from mice aged approximately 21 days. The cKO mice developed dilated cardiomyopathy and began experiencing sudden death at 40 days old, with no mutants surviving beyond 5 months.
2024-09-15 | E-MTAB-14440 | biostudies-arrayexpress
Project description:RationaleAn increase in cardiac afterload typically produces concentric hypertrophy characterized by an increase in cardiomyocyte width, whereas volume overload or exercise results in eccentric growth characterized by cellular elongation and addition of sarcomeres in series. The signaling pathways that control eccentric versus concentric heart growth are not well understood.ObjectiveTo determine the role of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in regulating the cardiac hypertrophic response.Methods and resultsHere, we used mice lacking all ERK1/2 protein in the heart (Erk1(-/-) Erk2(fl/fl-Cre)) and mice expressing activated mitogen-activated protein kinase kinase (Mek)1 in the heart to induce ERK1/2 signaling, as well as mechanistic experiments in cultured myocytes to assess cellular growth characteristics associated with this signaling pathway. Although genetic deletion of all ERK1/2 from the mouse heart did not block the cardiac hypertrophic response per se, meaning that the heart still increased in weight with both aging and pathological stress stimulation, it did dramatically alter how the heart grew. For example, adult myocytes from hearts of Erk1(-/-) Erk2(fl/fl-Cre) mice showed preferential eccentric growth (lengthening), whereas myocytes from Mek1 transgenic hearts showed concentric growth (width increase). Isolated adult myocytes acutely inhibited for ERK1/2 signaling by adenoviral gene transfer showed spontaneous lengthening, whereas infection with an activated Mek1 adenovirus promoted constitutive ERK1/2 signaling and increased myocyte thickness. A similar effect was observed in engineered heart tissue under cyclic stretching, where ERK1/2 inhibition led to preferential lengthening.ConclusionsTaken together, these data demonstrate that the ERK1/2 signaling pathway uniquely regulates the balance between eccentric and concentric growth of the heart.
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Project description:Gene Expression Analysis of Hypertrophic and Dilated Cardiomyopathy Associated TPM1 mutations in Engineered Heart Tissues
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Project description:Although concentric remodeling (CR) and concentric hypertrophy (CH) are common forms of left ventricular (LV) remodeling in heart failure with preserved ejection fraction (HFpEF), eccentric hypertrophy (EH) can also occur in these patients. However, clinical characteristics and outcomes of EH have not been well described in HFpEF. We prospectively studied 402 patients with HFpEF, divided into 4 groups based on LV structure: normal geometry (no LV hypertrophy [LVH] and relative wall thickness [RWT] ≤0.42); CR (no LVH and RWT >0.42); CH (LVH and RWT >0.42); and EH (LVH and RWT ≤0.42). We compared clinical, laboratory, echocardiographic, invasive hemodynamic, and outcome data among groups. Of 402 patients, 48 (12%) had EH. Compared with CH, patients with EH had lower systolic blood pressure and less renal impairment despite similar rates of hypertension. After adjustment for covariates, EH was associated with reduced LV contractility compared with CH: lower LVEF (β coefficient = -3.2; 95% confidence interval [CI] -5.4 to -1.1%) and ratio of systolic blood pressure to end-systolic volume (β coefficient = -1.0; 95% CI -1.5 to -0.5 mm Hg/ml). EH was also associated with increased LV compliance compared with CH (LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg β coefficient = 14.2; 95% CI 9.4 to 19.1 ml). Despite these differences, EH and CH had similarly elevated cardiac filling pressures and equivalent adverse outcomes. In conclusion, the presence of EH denotes a distinct subset of HFpEF that is pathophysiologically similar to HF with reduced EF (HFrEF) and may benefit from HFrEF therapy.
| S-EPMC3788852 | biostudies-literature
Project description:IntroductionThis study aimed to compare the efficacy of eccentrically focused resistance exercise (ECC RT) to concentrically focused resistance exercise (CNC RT) on knee osteoarthritis (OA) symptoms and strength.MethodsNinety participants consented. Participants were randomized to CNC RT, ECC RT, or a wait-list, no-exercise control group. Four months of supervised exercise training was completed using traditional weight machines (CNC RT) or modified-matched machines that overloaded the eccentric action (ECC RT). Main outcomes included one-repetition maximal strength (knee extension, leg flexion, and leg press), weekly rate of strength gain, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) total score and subscores.ResultsFifty-four participants (60-85 yr, 61% women) completed the study. Both CNC RT and ECC RT groups showed 16%-28% improvement relative to the wait-list, no-exercise control group (P = 0.003-0.005) for all leg strength measures. The rate of weekly strength gain was greater for CNC RT than for ECC RT for leg press and knee flexion (by 2.9%-4.8%; both, P < 0.05) but not knee extension (0.7%; P = 0.38). There were no significant differences in WOMAC total and subscores across groups over time. Leg press strength change was the greatest contributor to change in WOMAC total scores (R = 0.223). The change in knee flexion strength from baseline to month 4 was a significant predictor of the change in WOMAC pain subscore (F ratio = 4.84, df = 45, P = 0.032). Both modes of strength training were well tolerated.ConclusionsBoth resistance training types effectively increased leg strength. Knee flexion and knee extension muscle strength can modify function and pain symptoms irrespective of muscle contraction type. Which mode to pick could be determined by preference, goals, tolerance to the contraction type, and equipment availability.
| S-EPMC6746593 | biostudies-literature
Project description:Gene expression in the right ventricle is different in control patients as compared to either idiopathic dilated cardiomyopathy or pulmonary arterial hypertension Two human hearts obtained at autopsy from each of control, pulmonary hypertension, and dilated cardiomyopathy
2015-04-02 | E-GEOD-67492 | biostudies-arrayexpress