基础医学与临床 ›› 2025, Vol. 45 ›› Issue (7): 882-888.doi: 10.16352/j.issn.1001-6325.2025.07.0882

• 研究论文 • 上一篇    下一篇

血管生成素样蛋白8通过激活p53信号通路促进平滑肌细胞凋亡

于华惠, 杜智勇, 焦晓璐, 吕倩雯, 杨云云, 韩丽杰, 秦彦文*   

  1. 首都医科大学附属北京安贞医院 北京市心肺血管疾病研究所,北京 100029
  • 收稿日期:2025-04-23 修回日期:2025-05-21 出版日期:2025-07-05 发布日期:2025-06-24
  • 通讯作者: *qinyanwen@126.com
  • 基金资助:
    国家科技重大专项(2023ZD0503403,2023ZD0503400);北京市自然科学基金(7192030)

Angiopoietin-like protein 8 promotes apoptosis of vascular smooth muscle cells through activating p53 signaling pathway

YU Huahui, DU Zhiyong, JIAO Xiaolu, LYU Qianwen, YANG Yunyun, HAN Lijie, QIN Yanwen*   

  1. Beijing Institute of Heart Lung and Blood Vessel Disease,Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
  • Received:2025-04-23 Revised:2025-05-21 Online:2025-07-05 Published:2025-06-24
  • Contact: *qinyanwen@126.com

摘要: 目的 探究血管生成素样蛋白8(ANGPTL8)对血管平滑肌细胞(VSMCs)凋亡的作用机制。方法 采用血管紧张素Ⅱ (AngⅡ)处理人主动脉平滑肌细胞(HASMCs)建立体外腹主动脉瘤细胞模型,使用慢病毒感染HASMCs构建ANGPTL8敲低和ANGPTL8过表达稳转细胞株;TUNEL法观察细胞凋亡;Western blot测定HASMCs中ANGPTL8、caspase9、caspase3、Bcl-2、Bax、p53、PUMA的蛋白表达变化;RT-qPCR检测ANGPTL8、Bcl-2、Bax的mRNA表达变化。结果 AngⅡ可呈时间-剂量依赖性地显著刺激HASMC中ANGPTL8的蛋白表达(P<0.05); ANGPTL8敲低可显著减轻凋亡相关蛋白caspase9、caspase3及促凋亡蛋白Bax的表达,抑凋亡相关蛋白Bcl-2的表达显著升高(P<0.05); ANGPTL8过表达显著引起HASMC凋亡,使用p53通路抑制剂pifithrin-α(PFT-α) 处理后显著抑制由ANGPTL8过表达引起的凋亡反应。结论 ANGPTL8可能通过激活p53通路促进平滑肌细胞凋亡。

关键词: 血管生成素样蛋白8, 平滑肌细胞, 凋亡, p53信号通路

Abstract: Objective To investigate the mechanism by which angiopoietin-like protein 8 (ANGPTL8) regulates vascular smooth muscle cell (VSMCs) apoptosis. Methods An in vitro abdominal aortic aneurysm cell model was established by stimulating human VSMCs(HUSMCs) with angiotensin Ⅱ (AngⅡ). Stable ANGPTL8 knockdown and over-expression VSMC cell strains were generated using lentiviral transfection. TUNEL staining was used to detect apoptosis. Western blot analysis was performed to measure the protein expression of ANGPTL8, caspase9, caspase3, Bcl-2, Bax, p53, and PUMA, while RT-qPCR was used to assess mRNA expression of ANGPTL8, Bcl-2 and Bax. Results AngⅡ significantly induced ANGPTL8 expression in HVSMCs in a time- and dose-dependent manner(P<0.05). ANGPTL8 knockdown significantly reduced the expression of apoptosis-related proteins caspase9, caspase3, and Bax, while increased the expression of the anti-apoptotic protein Bcl-2(P<0.05). Conversely, ANGPTL8 over-expression markedly induced HVSMCs apoptosis, which was significantly suppressed by treatment with the p53 pathway inhibitor pifithrin-α (PFT-α). Conclusions ANGPTL8 may promote VSMC apoptosis by activation of p53 signaling pathway.

Key words: angiopoietin-like proteins 8, vascular smooth muscle cells, apoptosis, p53 pathway

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