miR-135a Regulates Atrial Fibrillation by Targeting Smad3.

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2023-01-01 DOI:10.1155/2023/8811996

Xueting Fan, Kai Feng, Yonghui Liu, Leixi Yang, Yizhuo Zhao, Liping Tian, Yiqun Tang, Xiaozhi Wang

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引用次数: 0

Abstract

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical. Atrial fibrosis is a hallmark feature of atrial structural remodeling in AF, which is regulated by the TGF-β1/Smad3 pathway. Recent studies have implicated that miRNAs are involved in the process of AF. However, the regulatory mechanisms of miRNAs remain largely unknown. This study is aimed at investigating the function and regulatory network of miR-135a in AF.

Methods: In vivo, the plasma was collected from patients with AF and non-AF subjects. Adult SD rats were induced by acetylcholine (ACh) (66 μg/ml)-CaCl₂ (10 mg/ml) to establish an AF rat model. In vitro, atrial fibroblasts (AFs), isolated from adult SD rats, were treated with high-frequency electrical stimulation (HES) (12 h) and hypoxia (24 h) to mimic the AF and atrial fibrosis, respectively. miR-135a expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-135a and Smad3 was speculated by the TargetScan database and confirmed by the luciferase reporter assay. Fibrosis-related genes, Smad3, and TRPM7 were all assessed.

Results: The expression of miR-135a was markedly decreased in the plasma of AF patients and AF rats, which was consistent with that in HES-treated and hypoxia-treated AFs. Smad3 was identified as a target of miR-135a. the downregulation of miR-135a was associated with the enhancement of Smad3/TRPM7 expressions in AFs. Additionally, the knockdown of Smad3 significantly reduced the expression of TRPM7 and further inhibited atrial fibrosis.

Conclusions: Our study demonstrates that miR-135a regulates AF via Smad3/TRPM7, which is a potential therapeutic target for AF.

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miR-135a通过靶向Smad3调控心房颤动

背景:心房颤动(AF)是临床上最常见的心律失常。心房纤维化是房颤心房结构重构的标志性特征，其受TGF-β1/Smad3通路调控。最近的研究表明，mirna参与了AF的发生过程。然而，mirna的调控机制在很大程度上仍不清楚。本研究旨在探讨miR-135a在房颤中的功能和调控网络。方法:在体内分别采集房颤患者和非房颤受试者的血浆。采用乙酰胆碱(ACh) (66 μg/ml)-CaCl2 (10 mg/ml)诱导成年SD大鼠建立AF大鼠模型。体外分离成年SD大鼠心房成纤维细胞(AF)，分别用高频电刺激(HES) (12 h)和缺氧(24 h)模拟AF和心房纤维化。通过实时定量聚合酶链反应(qRT-PCR)检测miR-135a的表达。TargetScan数据库推测miR-135a和Smad3之间的关联，并通过荧光素酶报告基因试验证实。纤维化相关基因、Smad3和TRPM7均被评估。结果:AF患者和AF大鼠血浆中miR-135a的表达明显降低，与hes和缺氧处理的AF一致。Smad3被确定为miR-135a的靶标。miR-135a的下调与AFs中Smad3/TRPM7表达的增强有关。此外，敲低Smad3显著降低TRPM7的表达，进一步抑制心房纤维化。结论:我们的研究表明miR-135a通过Smad3/TRPM7调控AF，这是AF的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.