Molecular biological approach to the pathogenesis of coronary spastic angina: A study on the role of p122 protein

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We demonstrated that Phospholipase C(PLC)-d1 activity in cultured skin fibroblasts from patients with coronary spastic angina(CSA) was enhanced, and found PLC-d1 864 G to A mutation in 10% of the male CSA patients. We also found p122 protein, cloned to potentiate PLC-d1 activity, and its gene expression level were enhanced in CSA. [Ca2+]i at baseline and the peak increase to acetylcholine were both higher in cells transfected with p122 than in those without p122. Further, we generated transgenic(TG) mice with the increased PLC-d1 activity specific to the VSMCs by inducing human R257H variant PLC-d1. Intravenous ergometrine induced ST segment elevation in homozygous TG. In isolated Langendorff-perfused hearts, coronary perfusion pressure was significantly increased in homozygous TG after ergometrine. Thus, the increased PLC-d1 activity causes the enhanced coronary vasomotility in TG. Both variant PLC-d1 and enhanced p122 protein were indicated to be involved in the pathogenesis of CSA.