Zhou Yupu, Guo Yongchuan
Department of Vascular Surgery, Jiangjin Centre Hospital, No. 725, Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing, Chongqing, 402260, China.
J Cardiothorac Surg. 2025 May 2;20(1):226. doi: 10.1186/s13019-025-03457-z.
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.
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.
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.
This research demonstrated that circ-PSMB1 might participate in AS development through regulating the pyroptosis of HAECs via the miR-624-3p/ASC axis.
动脉粥样硬化（AS）是一种由多种因素引起的心血管疾病，这些因素包括高血压、糖尿病、高脂血症和吸烟。据报道，环状RNA（circRNAs）参与了AS的进展。在此，我们研究了环状蛋白酶体20S亚基β1（PSMB1）参与AS的机制。
用氧化低密度脂蛋白（ox-LDL）刺激人主动脉内皮细胞（HAECs）以建立体外AS模型。采用MTT法检测细胞活力。用蛋白质免疫印迹法和qRT-PCR检测相关蛋白和mRNA表达。通过流式细胞术分析细胞焦亡。用商业试剂盒检测乳酸脱氢酶（LDH）水平。
我们发现，在用ox-LDL处理的HAECs中，circ-PSMB1和含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白（ASC）过表达，而miR-624-3p表达水平较低。circ-PSMB1沉默增强了细胞活力并减少了焦亡，这表现为白细胞介素-1β（IL-1β）和白细胞介素-18（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）蛋白表达的下调。此外，miR-624-3p抑制剂中和了si-circ-PSMB1的作用，ASC过表达中和了miR-624-3p模拟物在ox-LDL处理的HAECs中的作用。
本研究表明，circ-PSMB1可能通过miR-624-3p/ASC轴调节HAECs的焦亡来参与AS的发展。
