STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?
STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?
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DOI：
10.1042/cs20090449
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发表时间：
2009-12-15
期刊：
影响因子：
--
通讯作者：
Tostes RC
中科院分区：
文献类型：
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作者：
Giachini FR;Webb RC;Tostes RC
在流行病学研究中反复观察到高血压的性别相关差异。然而，赋予血管保护对女性的机制尚未完全阐明。细胞内Ca2+处理的性别相关差异，或者更具体地说，调节Ca2+进入血管平滑肌细胞的机制已被确定为高血压相关血管功能障碍的性别相关差异的参与者。最近，在细胞内储存耗尽的条件下，发现了调节Ca2+内流的新信号成分：基质相互作用分子1 (STIM1)，它作为细胞内Ca2+传感器；Orai1是Ca+2释放激活的Ca+2 （CRAC）通道的一个组成部分。这些蛋白一起重建了存储操作的Ca2+通道功能。STIM1/Orai1信号的紊乱与包括高血压在内的病理生理状况有关。在这篇综述中，我们分析了Ca2+处理的性别相关差异的证据，并提出了一个新的假设，即STIM/Orai信号的性别相关差异可能导致男性和女性受试者之间高血压相关血管的差异。
Sex-associated differences in hypertension have been repeatedly observed in epidemiological studies. However, the mechanisms conferring vascular protection to females are not totally elucidated. Sex-related differences in intracellular Ca2+ handling or, more specifically, in mechanisms that regulate Ca2+ entry into vascular smooth muscle cells have been identified as players in sex-related differences in hypertension-associated vascular dysfunction. Recently, new signaling components that regulate Ca2+ influx, in conditions of intracellular store depletion, were discovered: stromal interaction molecule 1 (STIM1), which works as an intracellular Ca2+ sensor; and Orai1, which is a component of the Ca+2 release-activated Ca+2 (CRAC) channels. Together, these proteins reconstitute store-operated Ca2+ channel function. Disturbances in STIM1/Orai1 signaling have been implicated in pathophysiological conditions, including hypertension. In this review we analyze evidence for sex-related differences in Ca2+ handling and propose a new hypothesis where sex-related differences in STIM/Orai signaling may contribute to hypertension-associated vascular differences between male and female subjects.