p122 Protein Enhances Intracellular Calcium Increase to Acetylcholine: Its Possible Role in the Pathogenesis of Coronary Spastic Angina
p122 Protein Enhances Intracellular Calcium Increase to Acetylcholine: Its Possible Role in the Pathogenesis of Coronary Spastic Angina
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DOI：
10.1161/atvbaha.110.203083
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Reiichi Murakami;T. Osanai;H. Tomita;Satoko Sasaki;Atsushi Maruyama;K. Itoh;Y. Homma;K. Okumura
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文献类型：
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作者：
Reiichi Murakami;T. Osanai;H. Tomita;Satoko Sasaki;Atsushi Maruyama;K. Itoh;Y. Homma;K. Okumura
冠状动脉痉挛患者的β-磷脂酶C-1活性增强，最近克隆了一种p122蛋白以增强磷脂酶C-1活性。为了研究p122在增强血管运动性中的作用，我们检测了培养的皮肤成纤维细胞中p122的表达，这些成纤维细胞来自冠状动脉痉挛和非冠状动脉痉挛的患者，在基线和用乙酰胆碱刺激后转染p122的细胞中的细胞内Ca 2+浓度（[Ca 2 +]i），以及基因组DNA中的启动子。方法和结果：11例冠状动脉痉挛患者p122蛋白和基因表达水平均高于9例对照组（P<0.01）。[Ca2+]i和乙酰胆碱引起的[Ca 2 +]i峰值增加均为转染p122细胞的2倍。相反，p122的敲低导致[Ca 2 +]i反应减弱。在p122启动子分析中，− 228 G/A和− 1466 C/T变体显示荧光素酶活性增加。虽然144例冠状动脉痉挛患者和148例对照组之间的− 1466 C/T变异相似，但男性患者的− 228 G/A变异比男性对照组更常见（P<0.05）。结论：p122蛋白在冠状动脉痉挛患者中上调，导致乙酰胆碱[Ca 2 +]i增加，因此似乎与冠状动脉血管运动性增强有关。
Objective—Phospholipase C-1 activity is enhanced in patients with coronary artery spasm, and a p122 protein was recently cloned to potentiate phospholipase C-1 activity. To investigate the role of p122 in enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular Ca2+ concentration ([Ca2+]i) at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA. Methods and Results—p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with levels in control subjects (n=9) (P<0.01 for both). [Ca2+]i at baseline and the peak increase in [Ca2+]i in response to acetylcholine were both 2 times higher in cells transfected with p122 than in those without p122. Conversely, knockdown of p122 resulted in diminished [Ca2+]i response. In the p122 promoter analysis, the −228G/A and −1466C/T variants revealed the increase in luciferase activity. Although the −1466C/T variant was similar between 144 patients with coronary spasm and 148 controls, the −228G/A variant was more frequent in male patients than in male controls (P<0.05). Conclusion—The p122 protein is upregulated in patients with coronary spasm, causing increased [Ca2+]i to acetylcholine, and thereby seems to be related to enhanced coronary vasomotility.