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

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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