Stem Cell Institute, Ankara University, Ankara, Turkey.
Biotechnology Institute, Ankara University, Ankara, Turkey.
Cardiovasc Ther. 2021 Oct 15;2021:5516185. doi: 10.1155/2021/5516185. eCollection 2021.
Transcriptomics of atrial fibrillation (AFib) in the setting of chronic primary mitral regurgitation (MR) remains to be characterized. We aimed to compare the gene expression profiles of patients with degenerative MR in AFib and sinus rhythm (SR) for a clearer picture of AFib pathophysiology.
After transcriptomic analysis and bioinformatics ( = 59), differentially expressed genes were defined using 1.5-fold change as the threshold. Additionally, independent datasets from GEO were included as meta-analyses.
QRT-PCR analysis confirmed that AFib persistence was associated with increased expression molecular changes underlying a transition to heart failure (, = 0.002; , = 0.002; , = 0.010), structural remodeling including changes in the extracellular matrix and cellular stress response (, = 0.003; , = 0.028; , = 0.038; , = 0.038), and cellular stress response (, = 0.038). Furthermore, AFib persistence was associated with decreased expression of the targets of structural remodeling (, = 0.021) and electrical remodeling (, = 0.035; , = 0.035) in both left and right atrial samples. The transmission electron microscopic analysis confirmed ultrastructural atrial remodeling and autophagy in human AFib atrial samples.
Atrial cardiomyocyte remodeling in persistent AFib is closely linked to alterations in gene expression profiles compared to SR in patients with primary MR. Study findings may lead to novel therapeutic targets. This trial is registered with ClinicalTrials.gov identifier: NCT00970034.
慢性原发性二尖瓣反流（MR）合并心房颤动（AFib）的转录组学特征仍有待确定。我们旨在比较 AFib 与窦性心律（SR）的退行性 MR 患者的基因表达谱，以更清楚地了解 AFib 的病理生理学。
经过转录组分析和生物信息学处理（=59），使用 1.5 倍变化作为阈值来定义差异表达基因。此外，还纳入了 GEO 的独立数据集进行荟萃分析。
实时定量 PCR 分析证实，AFib 的持续存在与分子变化的表达增加有关，这些变化是向心力衰竭转变的基础（，=0.002；，=0.002；，=0.010），包括细胞外基质和细胞应激反应的结构重塑（，=0.003；，=0.028；，=0.038；，=0.038），以及细胞应激反应（，=0.038）。此外，AFib 的持续存在与左、右心房样本中结构重塑（，=0.021）和电重塑（，=0.035；，=0.035）的靶基因表达降低有关。透射电镜分析证实了人 AFib 心房样本中的超微结构心房重塑和自噬。
与原发性 MR 患者的 SR 相比，持续性 AFib 中心房肌细胞重塑与基因表达谱的改变密切相关。研究结果可能为新的治疗靶点提供依据。该试验在 ClinicalTrials.gov 注册，标识符为：NCT00970034。
