Abstract 16464: Coronary Vasospasm Induced in Transgenic Mouse With Vascular Smooth Muscle-Specific Overexpression of p122RhoGAP/DLC1

Background: We previously reported that the activity of phospholipase C (PLC)-δ1, a key enzyme for Ca2+ signaling in the coronary artery, was 3-fold enhanced in patients with coronary spastic angina (CSA), and it was positively correlated with coronary vasomotility (JACC 2000). We further showed that p122RhoGAP/DLC1 protein, which was recognized as a stimulator of PLCδ-1, was upregulated in CSA patients (ATVB 2010). In the present study, we tested the hypothesis that enhanced expression of p122RhoGAP/DLC1 causes coronary spasm, by using mice with vascular smooth muscle-specific overexpression of p122RhoGAP/DLC1. Methods and Results: We generated transgenic mice overexpressing p122RhoGAP/ DLC1 protein under control of the mouse α-smooth muscle actin promoter (p122-Tg). The gene and protein expressions of p122RhoGAP/DLC1 were enhanced by 2-fold and 8-fold, respectively, in the aorta obtained from p122-Tg compared with wild type (WT) mice. Systolic blood pressure and pulse rate measured by tail-cuff method w...