High-density Lipoprotein Restrains The Down-Regulation Of Cystathionine Gama Lyase Induced By Oxidized Low-Density Lipoprotein In Vascular Smooth Muscle Cell

Objective: High density lipoprotein(HDL)could protect vascular endothelial cell and smooth muscle cell from the oxidative stress damage induced by Oxidized low density lipoprotein(ox-LDL). In this study, we would explore the effect of ox- LDL and HDL on cystathionine gamma-lyase(CSE) expression, the catalyst of gas signal molecule hydrogen sulfide in vascular smooth muscle cells(VSMCs),weather HDL could inhibit the effect of ox-LDL on CSE expression through suppressing oxidative stress and the mechanisms involved in.Methods: Rat aorta vascular smooth muscle cells were isolated in a germ-free environment. Healthy volunteers’ plasma were extracted and centrifuged to collect HDL and LDL. LDL was oxidized using copper sulfate(Cu SO4). The expression of CSE, heme oxygenase 1(HO-1) and the phospholation of ERK1/2, AKT, p38/MAPK in VSMCs were detected by western blot. CSE m RNA were assayed with fluorescence real time quantitative PCR.The release of intracellular reactive oxygen species(ROS) were detected with reactive oxygen detecting probe(DCFH- DA). The release of H2 S was measured with methylene blue coloration method. Interfered HO-1 expression in VSMCs with RNAi technology.Results: Ox-LDL decreased CSE protein and m RNA expression in a time- and dose- dependent manner. HDL not only could up-regulate CSE expression and the generation of H2 S in a time and dose dependent manner directly, but also could antagonize the down-regulation of CSE expression induced by ox-LDL. HDL could induce the activiation of ERK、AKT、p38/ MAPK pathway, ERK1/2、AKT、and p38/MAPK inhibitors could reduce HO-1 expression induced by HDL and ROS release induced by ox-LDL. ERK1/2、AKT、and p38/MAPK inhibitors could suppress CSE expression induced by HDL and the inhibitory of HDL to CSE expression induced by ox-LDL.Conclusion: HDL can not only antagonized the ROS release and the CSE reduction in VSMCs induced by ox-LDL through increasing HO-1 expression, but also directly induce CSE expression and H2 S release in VSMCs, and ERK1/2, AKT, p38/MAPK pathways were involved in these process.