The role of PLC and PKC in resistin-induced vascular smooth muscle cells proliferation pathway

Cardiovascular diseases (CVDs) are globally the leading cause of death and the underlying mechanisms vary on the diseases but mostly atherogenesis and developed thrombosis. Atherosclerosis which is characterized by endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation and migration, is a pathological process and occurs as result of atherogenic lipoproteins accumulation in arterial intima. Obesity and diabetes are two important risk factors for CVD. Since the adipokines are defined according to the results of the studies on obesity, adipose tissue is recognized as an endocrine organ. It has been suggested that newly discovered resistin plays an important role in various pathophysiological processes such as atherosclerosis by increasing endothelial dysfunction, vascular dysfunction, cardiac hypertrophy, migration and proliferation of VSMCs. Understanding of which signal pathways are involved in effects of resistin on VSMCs proliferation and migration, might provide an important advantage in preventing angiogenesis and the following pathophysiological conditions. In our study, we investigated the effects of the amount of NADPH oxidase-derived superoxide anion and phosphorylation of p44/42 MAPK and p38 MAPK resulted from PLC and PKC isoenzymes activation on proliferation pathway after incubation of resistin in VSMCs. Our results suggested that after resistin incubation, phosphorylation of PKC isoenzymes and activation of the other downstream pathways are dependent on activation of PLC in the proliferation pathway of VSMCs. PKC isoenzymes which are phosphorylated after activation of PLC are considered to have an important role in the proliferation pathway by p44/42 MAPK and produced of superoxide anion via NADPH oxidase activity. Key Words: Resistin, Vascular smooth muscle cell, PLC, PKC, p44/42 MAPK, ROS