TRPP2 associates with STIM1 to regulate cerebral vasoconstriction and enhance high salt intake-induced hypertensive cerebrovascular spasm
TRPP2 associates with STIM1 to regulate cerebral vasoconstriction and enhance high salt intake-induced hypertensive cerebrovascular spasm
复制标题
TRPP2联合STIM1调节脑血管收缩并增强高盐摄入诱发的高血压脑血管痉挛
DOI：
10.1038/s41440-019-0324-5
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发表时间：
2019-12-01
影响因子：
5.4
通讯作者：
Wang，Kai
中科院分区：
文献类型：
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作者：
Jiang，Wan;Ye，Li;Wang，Kai
脑血管痉挛是盐敏感性高血压患者的致命事件。储运钙进入（SOCE）与高血压血管收缩之间的关系尚未完全阐明。本研究探讨高盐摄入致高血压患者脑血管收缩反应的变化及SOCE主要成分多囊素-2 （TRPP2）、基质相互作用分子1 （STIM1）、Orai3的功能作用。多囊肾病2（编码TRPP2）基因敲除小鼠显示出ssoce诱导的脑血管收缩减少。采用无创尾袖容积脉搏波描记术每周监测与年龄匹配的正常或高盐饮食4周大鼠的血压。高盐饮食组的收缩压明显高于对照组。Western blotting和免疫组化结果显示，高血压大鼠脑血管TRPP2、STIM1和Orai3表达水平高于对照组。脑血管基底动脉张力测量显示，与对照组大鼠相比，高血压大鼠ssoc介导的收缩明显增加。此外，用SOCE抑制剂BTP-2 （10 μM）预处理或trpp2特异性或stim -特异性小干扰RNA转染的大鼠基底动脉中SOCE介导的收缩减少。采用2,3,5-三苯四氮唑（TTC）染色法定量测定鼠类缺血性脑卒中模型大脑中动脉闭塞24 h后脑梗死面积。高血压大鼠的脑梗死面积明显大于对照组，而btp -2治疗大鼠的脑梗死面积明显低于对照组。综上所述，这些发现表明，盐敏感高血压大鼠基底动脉中sce诱导的收缩可能过度活跃，提示TRPP2和SOCE及其其他成分的失调。
Cerebrovascular spasm is a life-threatening event in salt-sensitive hypertension. The relationship between store-operated calcium entry (SOCE) and vasoconstriction in hypertension has not been fully clarified. This study investigated the changes in cerebrovascular contractile responses in high salt intake-induced hypertension and the functional roles of the main components of SOCE, namely, polycystin-2 (TRPP2), stromal interaction molecule 1 (STIM1), and Orai3.Polycystic kidney disease 2(which encodes TRPP2) knockout mice displayed decreased cerebrovascular SOCE-induced contraction. The blood pressure of age-matched rats fed a normal or high-salt diet for 4 weeks was monitored weekly using noninvasive tail-cuff plethysmography. The systolic blood pressure of the rats fed a high-salt diet was significantly higher than that of controls. Western blotting and immunohistochemical results showed that these hypertensive rats expressed higher levels of cerebrovascular TRPP2, STIM1, and Orai3 than controls. Cerebrovascular tension measurements of the basilar artery indicated that SOCE-mediated contraction was significantly increased in hypertensive rats compared with control rats. In addition, SOCE-mediated contraction was decreased in the basilar arteries of rats pretreated with the SOCE inhibitor BTP-2 (10 μM) or transfected with TRPP2-specific or STIM1-specific small interfering RNA. Staining with 2,3,5-triphenyltetrazolium chloride (TTC) was used to quantify the infarcted brain area 24 h after middle cerebral artery occlusion, a model of ischemic stroke, in rodents. The infarcted brain area was significantly greater in hypertensive rats and significantly lower in BTP-2-treated rats than in controls. Taken together, these findings indicate that SOCE-induced contraction may be overactive in the basilar arteries of salt-sensitive hypertensive rats, suggesting the dysregulation of TRPP2 and SOCE and its other components.