Role of PKCd and ERK1/2 in trombin-stimulated vascular smooth muscle cells proliferation

Abstract

Cardiovascular disease is the greatestest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. Thrombin is involved in the differentiation and abnormal proliferation of VSMC associated with atherosclerosis and hypertension. Thrombin stimulation results in extracellular signal-regulated kinase (ERK1/2) activation through transactivation of the epidermal growth factor receptor (EGFR). Based on our reacent studies in which PD98059 used to inhibit ERK1/2, we have shown previously that ERK1/2 was involved in the regulation by thrombin of VSMC's proliferation. In addition, protein kinase C delta (PKCd) have also been detected in VSMC and shown to be regulated by thrombin. In this review, we are presenting literature data relating to role of PKCd and ERK1/2 in mediating the mitogenic action of thrombin in VSMC.