The key role of caveolin-1 in estrogen-mediated regulation of endothelial nitric oxide synthase function in cerebral arterioles in vivo.
The key role of caveolin-1 in estrogen-mediated regulation of endothelial nitric oxide synthase function in cerebral arterioles in vivo.
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Caveolin-1 在雌激素介导的体内脑小动脉内皮一氧化氮合酶功能调节中的关键作用。
DOI：
10.1097/00004647-200108000-00002
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Pelligrino,DA
中科院分区：
文献类型：
--
作者：
Xu,HL;Galea,E;Santizo,RA;Baughman,VL;Pelligrino,DA
卵巢切除术后脑血管内皮型一氧化氮合酶（eNOS）功能的显著损害可能与观察到脑血管eNOS及其内源性抑制剂小窝蛋白-1的丰度随雌激素状态的慢性变化而向相反方向变化有关。因此，作者建议通过独立操作切除卵巢的雌性大鼠中eNOS和小窝蛋白-1的表达，同时监测激动剂（乙酰胆碱）刺激的eNOS功能活性，来建立这些相关发现之间的联系。在目前的研究中，作者表明，单独上调eNOS（通过辛伐他汀治疗）或下调小窝蛋白-1（caveolin-1）（通过反义寡核苷酸给药）都不能恢复这些雌激素耗竭大鼠体内软脑膜小动脉中eNOS的功能。只有当eNOS上调和小窝蛋白-1下调相结合的活动正常化。这些结果建立了一个机制之间的联系，雌激素相关的多样性变化的丰富的小窝蛋白-1和eNOS蛋白和eNOS功能活性在脑小动脉。
The marked impairment in cerebrovascular endothelial nitric oxide synthase (eNOS) function that develops after ovariectomy may relate to the observation that the abundance of cerebral vascular eNOS and its endogenous inhibitor, caveolin-1, vary in opposite directions with chronic changes in estrogen status. The authors endeavored, therefore, to establish a link between these correlative findings by independently manipulating, in ovariectomized female rats, eNOS and caveolin-1 expression, while monitoring agonist (acetylcholine)-stimulated eNOS functional activity. In the current study, the authors showed that individually neither the up-regulation of eNOS (through simvastatin treatment), nor the down-regulation of caveolin-1 (through antisense oligonucleotide administration) is capable of restoring eNOS function in pial arteriolesin vivoin these estrogen-depleted rats. Only when eNOS up-regulation and caveolin-1 down-regulation are combined is activity normalized. These results establish a mechanistic link between the estrogen-associated divergent changes in the abundance of caveolin-1 and eNOS protein and eNOS functional activity in cerebral arterioles.