在慢性间歇性缺氧引起的血管内皮损伤中,NAD+生物合成减少介导的线粒体功能障碍的特定作用
1Clinical Biobank, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. songdongmei@hebmu.edu.cn.
European review for medical and pharmacological sciences
|November 17, 2023
概括
慢性间歇性缺氧 (CIH) 通过减少NAD+生物合成和引起线粒体功能障碍,损害内皮功能. 补充NAD+前体可能有助于治疗CIH诱导的血管损伤.
科学领域:
- 生物医学科学 生物医学科学
- 心血管研究研究心血管研究
- 线粒体生物学 线粒体生物学
背景情况:
- 心血管疾病 (CVD) 是阻塞性睡眠呼吸暂停 (OSA) 患者的主要死亡原因.
- 将OSA与心血管疾病联系在一起的确切机制尚不清楚,尽管有证据表明慢性间歇性缺氧 (CIH) 和高胆固醇饮食引起的明显动脉样硬化斑块特征.
- 已知CIH会导致血管内皮损伤.
研究的目的:
- 调查降低NAD+生物合成和随后的线粒体功能障碍是否介导CIH诱导的血管内皮损伤.
- 阐明NAD+代谢在CIH诱导的内皮功能障碍中的特定作用.
主要方法:
- 人类静脉内皮细胞 (HUVEC) 暴露于CIH和氧化低密度脂蛋白 (ox-LDL).
- 测量包括NAD+水平,NAMPT酶活性,线粒体功能 (ATP含量,膜潜力,呼吸链复合体活性),氧化应激和内皮功能 (血管收缩/扩张,粘附).
- 干预措施涉及NAD+前体补充 (NMN) 和NAD+合成抑制 (FK866).
主要成果:
- CIH抑制了NAMPT活性,降低了NAD+生物合成和NAD+/NADH比率.
- 在HUVEC中,CIH诱导了线粒体功能障碍,氧化应激增加,血管功能受损和粘附因子升高.
- 补充NMN恢复了由CIH损害的内皮细胞线粒体和整体功能.
- 氧-LDL诱导了内皮损伤,但没有影响NAD+路径指标,而NMN没有恢复氧-LDL诱导的损伤.
结论:
- CIH诱导的血管内皮损伤与NAD+生物合成减少和线粒体功能障碍有关.
- 通过前体补充增加NAD+水平可能为CIH相关的血管损伤提供治疗策略.
- 这种增强NAD+的方法在ox-LDL诱导的内皮损伤方面没有显著的益处.
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