Dataset Information

Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.

ABSTRACT:

Objective

This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients.

Methods

A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs.

Results

A total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634).

Conclusion

We found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.

SUBMITTER: Sun H

PROVIDER: S-EPMC8210924 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.

Sun Haoliang H Zhang Junjie J Shao Yongfeng Y

Anatolian journal of cardiology 20210601 6

<h4>Objective</h4>This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients.<h4>Methods</h4>A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length ( ...[more]

PMID: 34100729

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Project description:BackgroundProgressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency.MethodsConsecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency.ResultsIn training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm2) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study.ConclusionAmong 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.

Project description:BackgroundComplex fractionated atrial electrograms (CFAEs) may represent a phenomenon associated with sources of atrial fibrillation (AF) and are being used increasingly as targets of catheter ablation. However, current methods have limited efficacy for characterizing CFAEs important to substrate arrhythmogenicity and do not measure electrogram morphology.ObjectiveThe purpose of this study was to develop a methodology for quantifying the degree of morphologic heterogeneity in CFAE deflections, and to determine whether there are differences in this measurement between paroxysmal and persistent AF patients.MethodsTwo successive bipolar CFAEs of length 8.4 seconds each were acquired during AF from two sites each at the ostia of the four pulmonary veins (PVs) and from the anterior and posterior left atrial free wall in patients with paroxysmal AF (N = 10) and long-standing persistent AF (N = 10). Extrinsic and intrinsic features of electrogram shape were used to characterize fractionation in CFAE sequences. The extrinsic parameters were the amplitude, upslope, downslope, and width of each deflection. The intrinsic parameter was the voltage profile as characterized by the sum of absolute values. These measurements were compared to the mean interval between CFAE deflections, a standard fractionation indicator.ResultsThe variability of intrinsic/extrinsic morphologic parameters was higher in paroxysmal than persistent AF at the left superior PV (P < or =.003), the posterior left atrial free wall, anterior left atrial free wall, left inferior PV, and right superior PV (P <.05 for most parameters), and the right inferior PV (not significant). Mean CFAE deflection intervals were longer at all locations in paroxysmal AF but were significant only at the left superior PV and posterior left atrial free wall (P <.05). Quantitative morphologic parameters were not well correlated with dominant frequency (r(2) <0.32); thus, our new measures are robust to changes in activation rate.ConclusionA novel method for quantifying CFAEs, independent of activation rate, has been developed. The method demonstrates greater significance in the difference between CFAE morphology in paroxysmal and long-standing AF compared with mean interval between CFAE deflections. The differences identified suggest that CFAE morphology may evolve as AF persists.

Dataset Information

Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.

Objective

Methods

Results

Conclusion

Publications

Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.

Similar Datasets

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