Phospholipase Cγ1 Mediates Intima Formation Through Akt‐Notch1 Signaling Independent of the Phospholipase Activity

BackgroundVascular smooth muscle cell proliferation, migration, and dedifferentiation are critical for vascular diseases. Recently, it was demonstrated that Notch receptors have opposing effects on intima formation after vessel injury. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors. Methods and ResultsThere was a time‐ and dose‐dependent activation of Notch1 by angiotensin II and platelet‐derived growth factor in vascular smooth muscle cells. When phospholipase Cγ1 (PLCγ1) expression was reduced by small interfering RNA, Notch1 activation and Hey2 expression (Notch target gene) induced by angiotensin II or platelet‐derived growth factor were remarkably inhibited, while Notch2 degradation was not affected. Mechanistically, we observed an association of PLCγ1 and Akt, which increased after angiotensin II or platelet‐derived growth factor stimulation. PLCγ1 knockdown significantly inhibited Akt activation. Importantly, PLCγ1 phospholipas...