Clinical and molecular biological approach to the genesis of coronary artery spasm : A study on the role of p122 protein

p122蛋白最近被克隆以增强磷脂酶C（PLC）-δ1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，细胞内钙浓度（[Ca^<2+] i），细胞内钙浓度（[Ca^<2+] i）在基线和乙酰胆碱刺激后，转染p122的细胞，以及基因组DNA中的启动子。p122蛋白和基因表达水平在冠状动脉痉挛组（n=11）明显高于对照组（n=9）（均P<0.01）。[Ca p122转染的细胞中，基线时的[Ca^<2 +>] i和乙酰胆碱引起的[Ca^<2+>] i峰值增加都是未转染p122的细胞的两倍。在p122启动子分析中，-228G/A和-1466C/T变异体显示荧光素酶活性增加。-228G/A变异在男性患者中比在男性对照中更常见（p<0.05）。总之，p122在冠状动脉痉挛患者中上调，这导致乙酰胆碱[Ca^<2+>]_i增加，从而似乎与冠状动脉血管运动增强有关

A p122 protein was recently cloned to potentiate phospholipase C (PLC)-δ1 activity. To investigate the role of p122 in the enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular calcium concentration ([Ca^<2+>]_i) at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA. p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with that in control subjects (n=9) (both p<0.01). [Ca^<2+>]_i at baseline and the peak increase in [Ca^<2+>]_i in response to acetylcholine were both two times higher in cells transfected with p122 than in those without p122. In the p122 promoter analysis, the -228G/A and -1466C/T variants revealed the increase in luciferase activitiy. The -228G/A variant was more frequent in male patients than in male controls (p<0.05). In conclusions, p122 is upregulated in patients with coronary spasm, which causes increased [Ca^<2+>]_i to acetylcholine and thereby seems to be related to enhanced coronary vasomotility