降低了sarco/endoplasmic reticulum Ca(2+) 的吸收活性,可以解释高胆固醇血的子大动脉对NO的反应减少,但不是酸,但不是酸
T Adachi1, R Matsui, R M Weisbrod
1Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University Medical Center, Boston, MA, USA.
Circulation
|August 29, 2001
概括
高胆固醇血症通过降低/内分泌网膜 ATPase (SERCA) 功能而损害氧化 (NO) 的放松. 这项研究揭示了SERCA.
科学领域:
- 血管生物学 血管生物学
- 心血管生理学心血管生理学
- 顺滑肌肉药理学 顺滑肌肉药理学
背景情况:
- 高胆固醇血症 (HC) 影响内皮依赖放松,但对平滑肌肉对氧化 (NO) 反应的直接影响尚不清楚.
- 无介导放松涉及cGMP依赖和独立的途径,包括 (Ca2+) 处理由/内质网膜 ATPase (SERCA).
研究的目的:
- 调查cGMP和SERCA在高胆固醇 (HC) 子大脑中对NO和酸 (SNP) 的光滑肌肉反应受损中的作用.
主要方法:
- 使用瓜尼利基循环酶抑制剂和SERCA抑制剂 (cyclopiazonic acid,CPA) 来评估放松机制.
- 通过45Ca2+吸收和SERCA2蛋白表达在正常和HC子大动脉中测量了SERCA活性.
主要成果:
- SNP诱导的放松被 guanylyl cyclase 抑制剂取消,而NO诱导的放松只被部分抑制,其余的放松被 CPA 阻断.
- 在正常和HC大动脉中,CPA消除了剩余的NO诱导放松,但没有影响SNP诱导的放松.
- 尽管SERCA2蛋白水平没有变化,但SERCA活动在HC主动脉显著下降.
结论:
- 与SNP诱导的放松不同的是,NO诱导的放松部分是由cGMP独立的Ca2+吸收到sarco/endoplasmic网膜中介导的.
- 在高胆固醇血症中,SERCA功能的降低有助于血管光滑肌肉对NO的反应受损.
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