Cell Biology/Signaling p122 Protein Enhances Intracellular Calcium Increase to Acetylcholine Its Possible Role in the Pathogenesis of Coronary Spastic Angina

Objective—Phospholipase C1 activity is enhanced in patients with coronary artery spasm, and a p122 protein was recently cloned to potentiate phospholipase C1 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 Ca concentration ([Ca ]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). [Ca ]i at baseline and the peak increase in [Ca 2 ]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 [Ca ]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 [Ca ]i to acetylcholine, and thereby seems to be related to enhanced coronary vasomotility. (Arterioscler Thromb Vasc Biol. 2010;30:1968-1975.)