Effectiveness Of Atorvastatin Alone Or In Combination With Ezetimibe For Endoplasmic Reticulum Stress On Endothelial Cells

Background and objective: In recent years, the incidence and mortality of coronary heart disease has gradually increased. It is a serious hazard to human health.The dysfunction of vascular endothelial cells is an early stage of atherosclerosis formation. How to more effectively protect the vascular endothelial cells is the key to the prevention of atherosclerosis formation. Studies have shown that, endoplasmic reticulum stress plays an important role in the occurrence and development of atherosclerosis process. In atherosclerosis model, the expression of GRP78, GRP94 increases, but it is unclear whether the ERS participates in the process of vascular endothelial cells injury. Atorvastatin is widely used as anti-atherosclerosis drug,studies have shown that it can protect endothelial cells through activation of PI3KAKT-e NOs signaling pathway, but the mechanism about how to activate this pathway is unclear. Ezetimibe is a new lipid-lowering drug. Previous experiments show that ezetimibe combined with statin drugs have stronger lipid-lowering effect,it is unclear whether they will increase the protective effect to the vascular endothelial cells, and the mechanism of action is also unclear. The topic mainly researches the effectiveness of atorvastatin alone or in combination with ezetimibe for endoplasmic reticulum stress on endothelial cells of atherosclerosis formation,for further exploring the pathogenesis of atherosclerosis and finding a more ideal method to lay the theoretical foundation of atherosclerosis.Method: 1.Effectiveness of atorvastatin for endoplasmic reticulum stress by ox-LDL causing on HUVEC: By the methods of Rt-PCR and western blot to detect the expression of GRP78, ATF6, AKT at the m RNA and protein levels in the different treatment groups. 2.Effectiveness of atorvastatin and TUDCA forendoplasmic reticulum stress by ox-LDL causing on HUVEC: By the methods of Rt-PCR and western blot to detect the expression of GRP78, ATF6, AKT at the m RNA and protein levels in the different treatment groups. 3.Effectiveness of atorvastatin alone or in combination with ezetimibe for endoplasmic reticulum stress by ox-LDL causing on HUVEC: By the methods of Rt-PCR and western blot to detect the expression of GRP78, ATF6, AKT at the m RNA and protein levels in the different treatment groups. 4.We selected 60 patients, who have coronary atherosclerotic heart disease. They will be randomly divided into atorvastatin treatment group and atorvastatin combind with ezetimibe treatment group. Then the expression of GRP78, ATF6, AKT at protein levels in the different treatment groups was observed.Results: 1.Ox-LDL can increase the expression of GRP78, ATF6, AKT at m RNA level and the expression of GRP78, AKT at the protein level; Atorvastatin can cut the expression of GRP78, ATF6, AKT at m RNA level and the expression of GRP78, AKT at the protein level. 2.Both atorvastatin and TUDCA can cut the expression of GRP78, ATF6, AKT at m RNA level and the expression of GRP78,AKT at the protein level, and combination of two drugs has a stronger effect of cuting the expression. 3.Both atorvastatin and ezetimibe can cut the expression of GRP78, ATF6, AKT at m RNA level and the expression of GRP78, AKT at the protein level, and combination of two drugs has a stronger effect of cuting the expression. 4. Atorvastatin alone or in combination with ezetimibe can cut the expression of GRP78, ATF6, AKT in serum, but there was no significant difference between the two groups.Conclusion: 1.Ox-LDL can induce vascular endothelial cell endoplasmic reticulum stress.Atorvastatin has a stable endothelial cell ER stress effect,and it also can stablilize ER stress induced by ox-LDL.2.Both atorvastatin and TUDCA have stable endothelial cell ER stress effects, and combination of two drugs have a stronger effect of stablilizing ER stress.Their regulatory mechanism may be associated with AKT signaling pathway.3. In vitro experiments, ezetimibe has astable endothelial cell ER stress effect. Atorvastatin in combination with ezetimibe have a stronger effect of stablilizing endothelial cell ER stress.4. In vivo, atorvastatin alone and in combination with ezetimibe have suppressed the role of endoplasmic reticulum stress.