Circ-PSMB1敲低通过miR-624-3p/ASC轴抑制ox-LDL处理的人主动脉细胞的焦亡。

IF 1.5 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Yupu Zhou, Yongchuan Guo
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引用次数: 0

摘要

背景:动脉粥样硬化(AS)是一种由多种因素引起的心血管疾病,包括高血压、糖尿病、高脂血症和吸烟。环状rna (circRNAs)已被报道参与AS的进展。在这里,我们研究了环蛋白酶体20s亚基β 1 (PSMB1)参与AS的机制。方法:用氧化低密度脂蛋白(ox-LDL)刺激haec,建立体外AS模型。用MTT法测定细胞活力。Western blotting和qRT-PCR检测相对蛋白和mRNA的表达。流式细胞术分析细胞热凋亡情况。乳酸脱氢酶(LDH)水平用商用试剂盒检测。结果:我们发现,在ox-LDL处理的haec中,circ-PSMB1和含有CARD的凋亡相关斑点样蛋白(ASC)过表达,miR-624-3p低水平表达。通过下调IL-1β和IL-18 mRNA表达以及nod样受体热蛋白结构域相关蛋白3 (NLRP3)和GasderminD-N (GSDMD-N)蛋白表达,Circ-PSMB1沉默增强了细胞活力,减少了细胞焦亡。此外,miR-624-3p抑制剂可中和si-circ-PSMB1的作用,ASC过表达可中和ox- ldl处理的haec中miR-624-3p模拟物的作用。结论:本研究表明circ-PSMB1可能通过miR-624-3p/ASC轴调控HAECs的焦亡参与AS的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circ-PSMB1 knockdown inhibits the pyroptosis of ox-LDL treated human aortic cells via the miR-624-3p/ASC axis.

Background: Atherosclerosis (AS) is a cardiovascular disease that is caused by a variety of factors, including hypertension, diabetes, hyperlipidaemia and smoking. Circular RNAs (circRNAs) have been reported to participate in the progression of AS. Here, we investigated the mechanism by which circ-proteasome 20 S subunit beta 1 (PSMB1) participates in AS.

Methods: HAECs were stimulated with oxidized low-density lipoprotein (ox-LDL) to establish a model of AS in vitro. Cell viability was investigated with MTT assays. Western blotting and qRT‒PCR were used to measure relative protein and mRNA expression. Cell pyroptosis was analysed by flow cytometry. Lactate dehydrogenase (LDH) levels were measured with a commercial kit.

Results: We found that circ-PSMB1 and apoptosis-associated speck-like protein containing a CARD (ASC) were overexpressed and miR-624-3p was expressed at low levels in HAECs treated with ox-LDL. Circ-PSMB1 silencing enhanced cell viability and decreased pyroptosis, as shown by the downregulation of IL-1β and IL-18 mRNA expression as well as NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GasderminD-N (GSDMD-N) protein expression. In addition, the miR-624-3p inhibitor neutralized the effects of si-circ-PSMB1, and ASC overexpression neutralized the effects of the miR-624-3p mimic in ox-LDL-treated HAECs.

Conclusion: This research demonstrated that circ-PSMB1 might participate in AS development through regulating the pyroptosis of HAECs via the miR-624-3p/ASC axis.

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来源期刊
Journal of Cardiothoracic Surgery
Journal of Cardiothoracic Surgery 医学-心血管系统
CiteScore
2.50
自引率
6.20%
发文量
286
审稿时长
4-8 weeks
期刊介绍: Journal of Cardiothoracic Surgery is an open access journal that encompasses all aspects of research in the field of Cardiology, and Cardiothoracic and Vascular Surgery. The journal publishes original scientific research documenting clinical and experimental advances in cardiac, vascular and thoracic surgery, and related fields. Topics of interest include surgical techniques, survival rates, surgical complications and their outcomes; along with basic sciences, pediatric conditions, transplantations and clinical trials. Journal of Cardiothoracic Surgery is of interest to cardiothoracic and vascular surgeons, cardiothoracic anaesthesiologists, cardiologists, chest physicians, and allied health professionals.
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