Molecular Mechanism Of Acacetin Against Lysophosphatidylcholine-induced Apoptosis In Cultured Rat Aortic Vascular Smooth Muscle Cells

Introduction:Our recent study revealed that the major ox-LDL component lysophosphatidylcholine（lysoPC）induced a remarkable intracellular Ca²⁺ increase and apoptosis in primary cultured human coronary vascular artery smooth muscles cells（VSMCs）.In the present study,we investigate whether the natural flavone acacetin would inhibit the intracellular Ca²⁺ overload and apoptosis induced by lysoPC in primary cultured rat aortic VSMCs.Methods:Rat aortic VSMCs were primarily cultured for determining the effects of acacetin on Ca²⁺ influx,apoptosis,and related signal molecules induced by lysoPC with multiple biochemical and molecular biological approaches.Results:It was found that acacetin had no effect on intracellular Ca²⁺ overload induced by lysoPC;however,it antagonized lysoPC-induced cell apoptosis via increasing the anti-apoptotic protein Bcl-2,and decreasing the pro-apoptotic proteins Bax and cleaved caspase-3 expression.Additional experiments revealed that these effects were associated with upregulating the Nrf2 nuclear translocation,followed by increasing HO-1 and NQO-1,thereby reversing SOD-1 and catalase reduction and reducing reactive oxygen species（ROS）production induced by lysoPC.Silencing Nrf2 abolished the anti-apoptotic action and anti-oxidation effect of acacetin in primary cultured rat aortic VSMCs.Conclusions:Our results demonstrate for the first time that acacetin can suppress lysoPC-induced VSMCs apoptosis via reducing ROS production by activating Nrf2 anti-oxidation signaling pathways.Thus,acacetin may play an important role in preventing the pathophysiological process of disorders associated with apoptosis of VSMCs,such as atherosclerosis and restenosis.