内皮功能障碍的新机制:二甲基氨基氨酸二甲基氨基酸酶的失调
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Circulation
|June 22, 1999
概括
减少非对称二甲基氨基 (ADMA) 的降解,这是一种氧化合成酶 (NOS) 抑制剂,有助于高胆固醇血症中的内皮功能障碍. 这项研究研究了ADMA积累和二甲基氨酸二甲基胺酸酶 (DDAH) 在内皮细胞和子中的活性.
科学领域:
- 心血管研究研究心血管研究
- 内皮细胞生物学 内皮细胞生物学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 非对称二甲基氨基 (ADMA) 抑制氧化合成酶 (NOS),高血ADMA与高胆固醇和动脉样硬化有关.
- 降低ADMA降解被假定有助于在这些条件下ADMA积累.
研究的目的:
- 研究氧化LDL (oxLDL) 和瘤亡因子-α (TNF-α) 对内皮细胞中ADMA积累的影响.
- 检查这些因素对ADMA降解的酶二甲基氨酸二甲基氨基酶 (DDAH) 活性的影响.
- 在子模型中评估DDAH活性的活体高胆固醇血症.
主要方法:
- 转化的人类静脉内皮细胞 (ECV304) 用本地LDL,oxLDL或TNF-alpha进行治疗.
- 在条件介质中测量ADMA水平,使用高性能液态染色学.
- 通过西式斑点评估DDAH表达,并通过L-素素形成确定DDAH活性.
- 新西兰白被养正常或高胆固醇饮食以诱导高胆固醇血症.
主要成果:
- 氧化LDL和TNF-alpha显著增加了内皮细胞中的ADMA水平.
- 这种增加归因于减少的DDAH活性,而不是改变的DDAH表达.
- 子的高胆固醇血症导致大动脉,脏和肝脏中的DDAH活性显著降低.
结论:
- 高胆固醇血症中的内皮功能障碍可能是由于减少DDAH活性而导致ADMA降解受损的结果.
- 这些发现凸显了DDAH失调在高胆固醇血相关血管问题的病理生理学中的作用.
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