NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block.
Ontology highlight
ABSTRACT:
SUBMITTER: Lv X
PROVIDER: S-EPMC8627919 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Objective: We intended to explore the potential molecular mechanisms underlying cardiac conduction block inducted by UT-B deletion at the transcriptome level. Methods: The heart tissues were harvested from UT-B null mice and age-matched wild-type mice for lncRNA sequencing analysis. Based on the sequencing data, the differentially expressed mRNAs (DEMs) and lncRNAs (DELs) between UT-B knockout and control groups were identified, followed by function analysis and mRNA-lncRNA co-expression analysis. The miRNAs were predicted, and then the competing endogenous RNA (ceRNA) network was constructed. Results: UT-B deletion results in the aberrant expression of 588 lncRNAs and 194 mRNAs. These DEMs were significantly enriched in inflammation-related pathway. A lncRNA-mRNA co-expression network and a ceRNA network was constructed on the basis of the DEMs and DELs. C7 (complement C7)-NONMMUT137216.1 co-expression pair had the highest correlation coefficient in the co-expression network. NONMMUT140591.1 had the highest degree in ceRNA network and involved in ceRNA of NONMMUT140591.1-mmu-miR-298-5p-Gata5 (GATA binding protein 5). Conclusion: UT-B deletion may promote cardiac conduction block via inflammatory process. The ceRNA NONMMUT140591.1-mmu-miR-298-5p-Gata5 may be a potential molecular mechanism of UT-B knockout-induced cardiac conduction block.
2021-03-12 | GSE168717 | GEO
Project description:tableNONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block
| PRJNA713767 | ENA
Project description:ImportanceAlthough a high body mass index (BMI) has been found to be associated with increased risk of cardiac conduction block (CCB) in older adults, no further studies have investigated the association between obesity and CCB in the general population.ObjectiveTo investigate the association between obesity and CCB, including its subtypes.Design, setting, and participantsThis cohort study used data from participants in the Kailuan Study in China (2006-2018) who had completed a physical examination in 2006 (baseline) and had not experienced CCB before baseline. Data analysis was conducted from March to September 2023.ExposuresObesity status was defined by BMI in 3 groups: normal weight (18.5 to <24), overweight (24 to <28), and obesity (≥28).Main outcome and measuresThe primary outcome was CCB, which was diagnosed from standard 12-lead electrocardiography. The primary end point included high-grade atrioventricular block (HAVB), complete right bundle branch block, complete left bundle branch block, left anterior fascicular block (LAFB), and left posterior fascicular block. First-degree atrioventricular block (FAVB), second-degree type 1 AVB, HAVB, complete and incomplete right and left bundle branch block, LAFB, and left posterior fascicular block were considered separately as secondary end points.ResultsAmong 86 635 participants (mean [SD] age, 50.8 [11.9] years; 68 205 males [78.7%]), there were 33 259 individuals with normal weight (38.4%), 37 069 individuals with overweight (42.8%), and 16 307 individuals with obesity (18.8%). The mean (SD) follow-up was 10.6 (3.07) years. In the multivariable Cox proportional hazards regression analysis, obesity was associated with an increased risk of incident CCB (hazard ratio [HR], 1.21; 95% CI, 1.04-1.42) vs normal BMI. In secondary analysis, obesity was associated with an increased risk of FAVB (HR, 1.44; 95% CI, 1.21-1.73), HAVB (HR, 1.99; 95% CI, 1.03-3.82), and LAFB (HR, 1.29; 95% CI, 1.03-1.62) vs normal BMI. There was no association between obesity and other CCB subtypes. Obesity was associated with a greater increase in risk of CCB vs normal BMI in older (aged ≥65 years; HR, 1.44; 95% CI, 1.05-1.96) vs younger (aged <65 years; HR, 1.13; 95% CI, 0.96-1.34) participants (P for interaction < .001) and those with diabetes (HR, 2.16; 95% CI, 1.24-3.76) vs without diabetes (HR, 1.19; 95% CI, 1.02-1.39) (P for interaction = .02).Conclusions and relevanceThis study found that obesity was associated with an increased risk of CCB, with greater increases in risk for FAVB, HAVB, and LAFB. Individuals who were older and those who had diabetes had larger increases in risk.
| S-EPMC10644217 | biostudies-literature
Project description:BackgroundMethods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment - irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) - is highly desirable.Methodology/principal findingsWe investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s).Conclusion/significanceInhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.
| S-EPMC3340354 | biostudies-literature
Project description:Electrical impulse propagation is an essential function in cardiac, skeletal muscle, and nervous tissue. Abnormalities in cardiac impulse propagation underlie lethal reentrant arrhythmias, including ventricular fibrillation. Temporary propagation block throughout the ventricular myocardium could possibly terminate these arrhythmias. Electrical stimulation has been applied to nervous tissue to cause reversible conduction block, but has not been explored sufficiently in cardiac tissue. We show that reversible propagation block can be achieved in cardiac tissue by holding myocardial cells in a refractory state for a designated period of time by applying a sustained sinusoidal high-frequency alternating current (HFAC); in doing so, reentrant arrhythmias are terminated. We demonstrate proof of concept using several models, including optically mapped monolayers of neonatal rat ventricular cardiomyocytes, Langendorff-perfused guinea pig and rabbit hearts, intact anesthetized adult rabbits, and computer simulations of whole-heart impulse propagation. HFAC may be an effective and potentially safer alternative to direct current application, currently used to treat ventricular fibrillation.
| S-EPMC3328400 | biostudies-literature
Project description:Cardiac conduction system (CCS) disease, which results in disrupted conduction and impaired cardiac rhythm, is common with significant morbidity and mortality. Current treatment options are limited, and rational efforts to develop cell-based and regenerative therapies require knowledge of the molecular networks that establish and maintain CCS function. Recent genome-wide association studies (GWAS) have identified numerous loci associated with adult human CCS function, including TBX5 and SCN5A. We hypothesized that TBX5, a critical developmental transcription factor, regulates transcriptional networks required for mature CCS function. We found that deletion of Tbx5 from the mature murine ventricular conduction system (VCS), including the AV bundle and bundle branches, resulted in severe VCS functional consequences, including loss of fast conduction, arrhythmias, and sudden death. Ventricular contractile function and the VCS fate map remained unchanged in VCS-specific Tbx5 knockouts. However, key mediators of fast conduction, including Nav1.5, which is encoded by Scn5a, and connexin 40 (Cx40), demonstrated Tbx5-dependent expression in the VCS. We identified a TBX5-responsive enhancer downstream of Scn5a sufficient to drive VCS expression in vivo, dependent on canonical T-box binding sites. Our results establish a direct molecular link between Tbx5 and Scn5a and elucidate a hierarchy between human GWAS loci that affects function of the mature VCS, establishing a paradigm for understanding the molecular pathology of CCS disease.
| S-EPMC3386825 | biostudies-other
Project description:Background:Amyloidosis is caused by the deposition of abnormal proteins in the extracellular space of various organs. The clinical features of amyloidosis depend on the type of amyloid protein and the organ system involved. Case summary:A 51-year-old woman developed complete heart block which warranted a permanent pacemaker insertion. She was referred for evaluation of chronic pericardial effusion. The patient had stable vital signs and muffled heart sounds on examination of the cardiovascular system. Her chest X-ray film showed a permanent pacemaker in situ, and echocardiogram showed a chronic pericardial effusion without features of tamponade. On further evaluation, she was found to have an M band on serum electrophoresis, elevated free light chain ratio and amyloid deposits in bone marrow biopsy. Technetium pyrophosphate (Tc-PYP) scintigraphy was consistent with cardiac amyloidosis. Discussion:Cardiac amyloidosis can have diverse clinical presentations. Chronic pericardial effusion and conduction block can be a rare presentation of cardiac amyloidosis and needs to be considered while evaluating the same. Cardiac magnetic resonance imaging and Tc-PYP imaging can be used in establishing the diagnosis of cardiac amyloidosis, if endomyocardial biopsy is not feasible.
| S-EPMC6939806 | biostudies-literature
Project description:Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis, we induced 60-70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two pmp22 alleles (pmp22(+/-)). Induction time for the CB was significantly shorter in pmp22(+/-) mice than that in pmp22(+/+) mice. This shortened induction was also found in myelin-associated glycoprotein knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin. Pmp22(+/-) nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [(3)H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.
| S-EPMC3676309 | biostudies-literature
Project description:BACKGROUND:Right ventricular (RV) pacing-induced cardiomyopathy (PICM) occurs in ?30% of patients with RV leads. This study evaluated the long-term effects of restoring antegrade conduction with a biological pacemaker in a porcine model of RV PICM. OBJECTIVES:The goal of this study was to determine if antegrade biological pacing can attenuate RV PICM. METHODS:In pigs with complete atrioventricular (AV) block, transcription factor T-box 18 (TBX18) was injected into the His bundle region in either of 2 experimental protocols: protocol A sought to prevent PICM, and protocol B sought to reverse PICM. In protocol A, we injected adenoviral vectors expressing TBX18 (or the reporter construct green fluorescent protein) after AV node ablation, and observed the animals for 8 weeks. In protocol B, PICM was established by using AV node ablation and 4 weeks of electronic RV pacing, at which point TBX18 was injected into the His bundle region. RESULTS:In protocol A, TBX18 biological pacing led to superior chronotropic support (62.4 ± 3 beats/min vs. 50.4 ± 0.4 beats/min; p = 0.01), lower backup pacemaker utilization (45 ± 2.6% vs. 94.6 ± 1.4%; p = 0.001), and greater ejection fraction (58.5 ± 1.3% vs. 46.7 ± 2%; p = 0.001). In protocol B, full-blown RV PICM was evident 4 weeks after complete AV block in both groups; subsequent intervention led to higher mean heart rate (56 ± 2 beats/min vs. 50.1 ± 0.4 beats/min; p = 0.05), less backup pacemaker utilization (53 ± 8.2% vs. 95 ± 1.6%; p = 0.003), and a greater ejection fraction (61.7 ± 1.3% vs. 49 ± 1.6%; p = 0.0003) in TBX18-injected animals versus control animals. CONCLUSIONS:In a preclinical model, pacemaker-induced cardiomyopathy can be prevented, and reversed, by restoring antegrade conduction with TBX18 biological pacing.
| S-EPMC6726386 | biostudies-literature
Project description:A significant number of right bundle branch block (RBBB) patients receive cardiac resynchronization therapy (CRT), despite lack of evidence for benefit in this patient group. His bundle (HBP) and left bundle pacing (LBP) are novel CRT delivery methods, but their effect on RBBB remains understudied. We aim to compare pacing-induced electrical synchrony during conventional CRT, HBP, and LBP in RBBB patients with different conduction disturbances, and to investigate whether alternative ways of delivering LBP improve response to pacing. We simulated ventricular activation on twenty-four four-chamber heart geometries each including a His-Purkinje system with proximal right bundle branch block (RBBB). We simulated RBBB combined with left anterior and posterior fascicular blocks (LAFB and LPFB). Additionally, RBBB was simulated in the presence of slow conduction velocity (CV) in the myocardium, left ventricular (LV) or right ventricular (RV) His-Purkinje system, and whole His-Purkinje system. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (BIVAT-90). Compared to baseline, HBP significantly improved activation times for RBBB alone (BIVAT-90: 66.9 ± 5.5 ms vs. 42.6 ± 3.8 ms, p < 0.01), with LAFB (69.5 ± 5.0 ms vs. 58.1 ± 6.2 ms, p < 0.01), with LPFB (81.8 ± 6.6 ms vs. 62.9 ± 6.2 ms, p < 0.01), with slow myocardial CV (119.4 ± 11.4 ms vs. 97.2 ± 10.0 ms, p < 0.01) or slow CV in the whole His-Purkinje system (102.3 ± 7.0 ms vs. 75.5 ± 5.2 ms, p < 0.01). LBP was only effective in RBBB cases if combined with anodal capture of the RV septum myocardium (BIVAT-90: 66.9 ± 5.5 ms vs. 48.2 ± 5.2 ms, p < 0.01). CRT significantly reduced activation times in RBBB in the presence of severely slow RV His-Purkinje CV (95.1 ± 7.9 ms vs. 84.3 ± 9.3 ms, p < 0.01) and LPFB (81.8 ± 6.6 ms vs. CRT: 72.9 ± 8.6 ms, p < 0.01). Both CRT and HBP were ineffective with severely slow CV in the LV His-Purkinje system. HBP is effective in RBBB patients with otherwise healthy myocardium and Purkinje system, while CRT and LBP are ineffective. Response to LBP improves when LBP is combined with RV septum anodal capture. CRT is better than HBP only in patients with severely slow CV in the RV His-Purkinje system, while CV slowing of the whole His-Purkinje system and the myocardium favor HBP over CRT.
| S-EPMC9532840 | biostudies-literature