Apolipoprotein-J Prevents OX-LDL Induced Apoptosis In Neonatal Rat Ventricular Cell

Cardiovascular disease is a kind of disease in modern society which is a serious threat to human health,including atherosclerosis(atherosclerosis,AS),hypertension,ischemic cardiomyopathy.Atherosclerosis is a common pathological basis of all cardiovascular diseases.In recent years,a large number of domestic and foreign research shows that many risk factors of coronary heart disease can lead to a variety of cellular components in the vascular wall had more active oxygen(reactive oxygen species,ROS),causing the pathophysiology of atherosclerosis by reactive oxygen species,such as the oxidative modification of LDL oxidation of low density.Lipoprotein(oxidized low density lipoprotein,ox-LDL),low density lipoprotein(low density,lipoprotein,LDL)of the oxidation products in the occurrence of atherosclerosis,plays an important role in the development,can cause the damage of vascular endothelium,activation of cells to produce cytokines,and induce apoptosis.Apolipoprotein J(Apolipoprotein-J,ApoJ)is a multifunctional glycoprotein widely present in tissues and body fluids..It can be involved in sperm maturation,tissue remodeling,and complement activation and regulation of physiological and pathological processes,but also can play a role in apoptosis and lipid transport.Meanwile,Apolipoprotein J plays an important role in the inhibition of apoptotic cells.So it can protect the cells damaged by heart.However,the relationship between apolipoprotein J and ox-LDL plays an important role in the growth and death of cardiomyocytes,which has not been paid enough attention.Objective: to further clarify the signal transduction mechanism of effects of ox-LDL on myocardial cells and cells,and to evaluate the protective effects of ApoJ against the cytotoxicity of ox-LDL in neonatal rat ventricular cells(NRVCs).Methods :ApoJ expression was achieved by infection with recombinant adenovirus in NRVCs.Cultured neonatal rat ventricular myocytes(NRVMs)were incubated with ox-LDL for 24 hours,or preincubated with LOX-1 neutralizing antibody(TS92),ROS scavenger(Mn(ⅡI)TBAP,pCaMKⅡ inhibitor(KN93)for 1 hour.Cell injury was analyzed by MTT and Caspase-3/7 assay kits and Lox-1,Nox2/gp91 phox,oxCaMKⅡ,p47 expressions were detected using Western-blot analysis.Results:In culture,NRVCs were damaged by exposure to ox-LDL evidenced by increased caspase3/7 acitivity,enhanced caspase-3 expression and decreased cell viability,meanwhile,ApoJ overexpression using an adenovirus vector significantly reduced the ox-LDL-induced cell injury.ApoJ also preventedox-LDL from augmenting ROS production demonstrated by elevated Nox2/gp91 phox and P47 expression.Furthermore,ApoJ overexpression decreased the expression of CaMKⅡδ caused by ox-LDL in cultured NRVCs,and upregulation of CaMKⅡ activity mediated by ox-LDL were significantly inhibited by overexpression of ApoJ.Meanwhile,the CaMKⅡ inhibitor KN93 diminished the antioxidant effects of ApoJ,and prevented the protective effect of ApoJ against the cytotoxicity of ox-LDL.However,the reactive oxygen species(ROS)scavenger,Mn(ⅡI)TBAP,also attenuated the increased expression and activity of CaMKⅡδ induced by ox-LDL,and showed similar results of ApoJ by attenuating ox-LDL-induced cell damage as ApoJ did.Conclusions: 1.ApoJ plays a role in reducing myocardium cell apoptosis induced by ox-LDL.2.ox-LDL may induces cell injury via activating LOX-1/ROS/oxCaMKⅡ pathways.3.ApoJ mediates cardioprotection by against cytotoxicity of ox-LDL through the ROS-CaMKⅡ pathways.