Dataset Information

In-depth quantitative proteomic analysis of rat cardiac tissue for exploring potential mediators of early cardiac reaioablation effect

ABSTRACT: Recently, stereotactic ablative radiotherapy (SABR) is adopted to noninvasively treat catheter ablation-refractory ventricular tachycardia (VT). VT episodes were dramatically reduced after SABR within few weeks, but underlying mechanisms of these clinical effects as well as potential mediator of early antiarrhythmic effects were unknown

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Cardiocyte

SUBMITTER: Dohyun Han

LAB HEAD: Dohyun Han

PROVIDER: PXD030878 | Pride | 2022-08-12

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20200523_1WEEK_VEN_TMT10_F1.raw	Raw
	20200523_1WEEK_VEN_TMT10_F10.raw	Raw
	20200523_1WEEK_VEN_TMT10_F11.raw	Raw
	20200523_1WEEK_VEN_TMT10_F12.raw	Raw
	20200523_1WEEK_VEN_TMT10_F13.raw	Raw

Items per page:

1 - 5 of 51

Publications

One-Week Dynamic Changes in Cardiac Proteomes After Cardiac Radioablation in Experimental Rat Model.

Kim Byoung Hyuck BH Jung Jin Woo JW Han Dohyun D Cha Myung-Jin MJ Chang Ji Hyun JH

Frontiers in cardiovascular medicine 20220628

<h4>Background</h4>Recently, stereotactic ablative radiotherapy (SABR) has been adopted to non-invasively treat catheter ablation-refractory ventricular tachycardia (VT). VT episodes have been dramatically reduced after SABR, within weeks; however the underlying mechanisms of these clinical effects and potential mediators of early anti-arrhythmic effect remain unclear.<h4>Methods</h4>In this study, cardiac tissue was harvested from non-irradiated control (0 Gy), conventional irradiated control ( ...[more]

PMID: 35837601

Similar Datasets

Project description:Aims: A mutation in the phospholamban (PLN) gene, leading to deletion of Arg14 (R14del), has been associated with malignant arrhythmias and ventricular dilation. Identifying pre-symptomatic carriers with vulnerable myocardium is crucial because arrhythmia can result in sudden cardiac death, especially in young adults with PLN-R14del mutation. This study aimed at assessing the efficiency and efficacy of in vivo genome editing, using CRISPR/Cas9 and a cardiotropic adeno-associated virus (AAV9), in improving cardiac function in young adult mice expressing the human PLN-R14del. Methods and Results: Humanized mice were generated expressing human wild-type (hPLN-WT) or mutant (hPLN-R14del) PLN in the heterozygous state, mimicking human carriers. Cardiac magnetic resonance imaging at 12 weeks of age showed bi-ventricular dilation and increased stroke volume in mutant vs. WT mice, with no deficit in ejection fraction or cardiac output. Challenge of ex vivo hearts with isoproterenol and rapid pacing unmasked higher propensity for sustained ventricular tachycardia (VT) in hPLN-R14del relative to hPLN-WT. Specifically, the VT threshold was significantly reduced (20.3±1.2 Hz in hPLN-R14del vs. 25.7±1.3 Hz in WT, p<0.01) reflecting higher arrhythmia burden. To inactivate the R14del allele, mice were tail-vein-injected with AAV9.CRISPR/Cas9/gRNA or AAV9 empty capsid (controls). CRISPR-Cas9 efficiency was evaluated by droplet digital PCR and NGS-based amplicon sequencing. In vivo gene editing significantly reduced end diastolic and stroke volumes in hPLN-R14del CRISPR-treated mice compared to controls. Susceptibility to VT was also reduced, as the VT threshold was significantly increased relative to controls (30.9±2.3 Hz vs. 21.3±1.5 Hz; p<0.01). Conclusions: This study is the first to show that disruption of hPLN-R14del allele by AAV9- CRISPR/Cas9 improves cardiac function and reduces VT susceptibility in humanized PLN-R14del mice, offering preclinical evidence for translatable approaches to therapeutically suppress the arrhythmogenic phenotype in human patients with PLN-R14del disease.