高表达Nrf2的骨髓间充质干细胞外泌体对心房颤动大鼠心脏纤维化的抑制作用

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2022-03-15 DOI:10.1155/2022/2687807

Lijuan Xu, Yingchao Fan, Liting Wu, Cui Zhang, Min Chu, Yuan Wang, Wenfang Zhuang

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引用次数: 8

摘要

背景尽管核因子-红系2相关因子2（Nrf2）信号传导与多种心脏病的发病机制有关，但关于Nrf2在心房颤动（AF）中的作用的数据仍然很少。本研究的目的是分析Nrf2在AF大鼠骨髓间充质干细胞（BMSC）来源的外泌体中的过表达作用。方法从对照或Nrf2慢病毒转导的BMSC中收集外泌体，然后通过尾静脉注射到AF大鼠体内。使用心电图观察AF持续时间。免疫组织化学染色用于评估心房心肌组织中Nrf2、HO-1、α-SMA、I型胶原或TGF-β1的表达谱。相反，Masson染色用于评估心房纤维化，而心肌内的细胞凋亡通过TUNEL测定进行评估。此外，通过ELISA评估TNF-α、IL-1β、IL-4或IL-10的血清表达。结果本研究结果显示心房颤动大鼠心肌内Nrf2/HO-1明显下调。发现对照或Lv-Nrf2外泌体的注射显著减轻和降低AF时间跨度，同时减少心肌细胞凋亡。此外，注射Lv-Nrf2外泌体显著降低了AF大鼠心房纤维化，并抑制了炎症反应。结论使用过表达的Nrf2递送BMSC衍生的外泌体可通过Nrf2/HO-1通路触发抑制AF诱导的心律失常、心肌纤维化、细胞凋亡和炎症。

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Exosomes from Bone Marrow Mesenchymal Stem Cells with Overexpressed Nrf2 Inhibit Cardiac Fibrosis in Rats with Atrial Fibrillation

Background Even though nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling has been associated with the pathogenesis of multiple heart conditions, data on roles of Nrf2 within atrial fibrillation (AF) still remain scant. The present investigation had the aim of analyzing Nrf2-overexpressing role/s upon bone mesenchymal stem cell- (BMSC-) derived exosomes in rats with AF. Methods Exosomes were collected from control or Nrf2 lentivirus-transduced BMSCs and then injected into rats with AF through the tail vein. AF duration was observed using electrocardiography. Immunohistochemical staining was then employed for assessing Nrf2, HO-1, α-SMA, collagen I, or TGF-β1 expression profiles within atrial myocardium tissues. Conversely, Masson staining was utilized to evaluate atrial fibrosis whereas apoptosis within myocardia was evaluated through TUNEL assays. In addition, TNF-α, IL-1β, IL-4, or IL-10 serum expression was assessed through ELISA. Results Results of the current study showed significant downregulation of Nrf2/HO-1 within AF rat myocardia. It was found that injection of the control or Lv-Nrf2 exosomes significantly alleviated and lowered AF timespans together with reducing cardiomyocyte apoptosis. Moreover, injection of Lv-Nrf2 exosomes essentially lowered AF-driven atrial fibrosis and also inhibited inflammatory responses in the rats with AF. Conclusion Delivery of BMSC-derived exosomes using overexpressed Nrf2 inhibited AF-induced arrhythmias, myocardial fibrosis, apoptosis, and inflammation via Nrf2/HO-1 pathway triggering.

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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.