一个自我实现的预言:C-反应蛋白减弱氧化的产生,并抑制血管新生
Subodh Verma1, Chao-Hung Wang, Shu-Hong Li
1Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada. subodh.verma@sympatico.ca
Circulation
|August 21, 2002
概括
通过影响内皮NO合成酶 (eNOS) 的mRNA稳定性,C反应蛋白 (CRP) 直接减少氧化 (NO) 的产生. 这种降低的NO生物可用性会损害血管生成,并可能导致心血管疾病.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 炎症研究 炎症研究
背景情况:
- 氧化 (NO) 在心血管健康和疾病中起着关键作用.
- C-反应蛋白 (CRP) 是心血管事件的强有力的预测剂.
- 需要阐明CRP和NO生产之间的关系.
研究的目的:
- 调查CRP是否影响氧化 (NO) 生产.
- 确定CRP影响NO合成的分子机制.
- 评估CRP对内皮细胞功能和血管生成的影响.
主要方法:
- 化内皮细胞 (ECs) 具有不同度的重组CRP.
- 测量NO和循环氨酸单酸盐 (cGMP) 产量.
- 对内皮NO合成酶 (eNOS) mRNA和蛋白质表达和mRNA稳定性的分析.
- 评估EC存活率,细胞亡,迁移和体外血管生成.
主要成果:
- CRP显著抑制基底和刺激NO和cGMP从ECs中的释放.
- CRP降低了eNOS mRNA和蛋白质的表达,主要是通过减少mRNA稳定性.
- CRP降低了基底和VEGF刺激的血管生成,并促进了NO依赖的EC亡.
结论:
- 通过对eNOSmRNA的转录后调节,CRP直接抑制NO的产生.
- 由于CRP而降低的NO生物可用性会损害血管新生,这是一个关键的补偿机制.
- 通过CRP介导的NO合成减少可能会导致心血管疾病的发展.
- 针对血CRP水平的治疗策略可以提高NO的生物可用性并降低心血管风险.
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