诺克斯1/PAK1是血管炎症II诱导的血管炎症和腹腔大动脉动脉瘤形成所需的
Hui He1, Tianyu Jiang1, Meng Ding1
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guizhou Medical University, Gui'an, 561113, Guizhou, PR China.
Redox biology
|December 25, 2024
概括
在光滑肌细胞中缺少NADPH氧化酶1 (Nox1) 减少腹腔大动脉动脉瘤 (AAA) 的形成,通过抑制血管炎症和细胞外矩阵重塑. 诺克斯1与PAK1相互作用,推动AAA的进展.
科学领域:
- 心血管生物学 心血管生物学
- 血管生物学 血管生物学
- 分子医学是分子医学.
背景情况:
- NADPH氧化酶1 (Nox1) 是血管光滑肌细胞 (VSMC) 中的一个关键酶.
- 大细胞中央激活和细胞外矩阵 (ECM) 重塑有助于腹腔大动脉瘤 (AAA) 的发展.
- 在AAA病原体中Nox1的特定作用尚未完全阐明.
研究的目的:
- 调查Nox1在血管素II (Ang II) 诱导的AAA进展中的作用.
- 探索涉及Nox1在VSMC激活和ECM重塑中的潜在分子机制.
- 在AAA中确定Nox1和p21激活激酶1 (PAK1) 之间的相互作用.
主要方法:
- 使用的ApoE-/-Nox1SMCko小鼠具有光滑肌肉细胞特异的Nox1.1删除.
- 进行Ang II输注28天以诱导AAA.
- 评估了AAA形成,生存率,活性氧物种 (ROS) 水平,炎症细胞透,ECM降解 (弹性素碎片),矩阵金属蛋白酶 (MMP) 活性和分子信号通路 (PAK1,MAPKs,NF-κB,Sp1).
主要成果:
- 特定于SMC的Nox1删除显著降低了AAA发病率和改善了生存率.
- 诺克斯1缺乏减少了大动脉ROS,单细胞/巨细胞透,弹性素碎片化和MMP活性.
- 诺克斯1与PAK1相互作用,通过ROS信号传递促进VSMC的增殖,迁移和分化,导致MAPK和NF-κB激活,以及Sp1介导的MMP2表达.
结论:
- 诺克斯1在促进Ang II诱导的AAA形成方面发挥着至关重要的作用.
- 在AAA中,Nox1/PAK1轴驱动VSMC激活,血管炎症和ECM重塑.
- 准Nox1可能代表AAA的治疗策略.
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