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Microsecond pulsed electric fields induce myocardial ablation by damaging mitochondria

ABSTRACT: Catheter ablation is an effective treatment to prevent recurrence of Atrial fibrillation (AF) and can be used to maintain sinus rhythm and improve symptoms of AF, but to some extent it can cause a range of adverse effects associated with catheter ablation. Pulsed electric field is a newer treatment modality to replace catheter ablation for atrial fibrillation due to its fewer side effects. Different from radiofrequency ablation, which destroys diseased myocardial tissue by thermal energy, pulsed electric field ablation achieves the purpose of atrial fibrillation ablation by inducing damage to diseased myocardial cells through irreversible electroporation. However, some experimental parameters and mechanism of pulsed electric fields remain unclear.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE214387 | GEO | 2023/11/30

REPOSITORIES: GEO

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Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation

Project description:Background: Genomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess whether this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation. Methods: mRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAA) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n=83) or in LAA cardiomyocytes (n=52), and combined with clinical parameters to predict AF recurrence. Literature suggests bone morphogenetic protein 10 (BMP10) as a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with eleven cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients. Results: Reduced cardiomyocyte PITX2 concentrations, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, qPCR and Western blotting confirmed BMP10 as one of most PITX2-repressed atrial genes. Left atrial size (hazard ratio per mm increase, HR [95%CI] 1.055 [1.028, 1.082], non-paroxysmal AF (HR 1.672 [1.206, 2.318]) and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed eleven other cardiovascular biomarkers in predicting recurrent AF. Conclusions: Reduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted, atrial protein BMP10 identify patients at risk of recurrent AF after ablation.

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Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AF，which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarray，focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation.

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Array-based genome-wide transcriptome analysis of the left atrial appendage for the difference between SR maintenance group and AF recurrence group

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