Study On The Anti-inflammatory Mechanism Of High Density Lipoprotein In Patients With Premature Coronary Artery Disease

Objective:The purpose of this study is to investigate the inflammatory effect of high density lipoprotein(HDL)in premature coronary artery disease(PCAD)patients and in healthy subjects on human umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL)in vitro and to explore the possible mechanism of this effect.It not only can further clarify the pathogenesis of premature coronary artery disease,but also can provide a new idea for clinical prevention and treatment of premature coronary artery disease.Methods:1.Blood samples of healthy subjects(male <55 years,female <65 years)and premature coronary artery disease patients(male <55 years,female <65 years)according to the experimental conditions were collected and HDL was isolated from the blood samples.2.The expression of inflammatory cytokines such as intercellular cell adhesion molecule-1(ICAM-1),tumor necrosis factor-?(TNF-?),high mobility group protein box1(HMGB-1),receptor for advanced glycation end product(RAGE)were detected by Elisa and Western Blot incubated with ox-LDL after different time to identify the most significant time of the inflammatory response.3.After HUVECs were incubated with different concentrations of HDL for the corresponding time,the inflammatory molecules and inflammatory pathway molecules were detected to clear the most significant concentration of anti-inflammatory effect ofHDL.4.The anti-inflammatory effects of the HDL group of healthy subjects and the HDL group of patients with premature coronary artery disease were compared.Results:1.The inflammatory response of HUVECs can be induced by 50mg/L ox-LDL.The levels of HMGB-1,TNF-? and ICAM-1 in the supernatant of the cells increased with the prolongation of time and reached the peak at 48 hours(P <0.05).The expressions of HMGB-1 and RAGE protein were increased and reached the peak at 24 hours while decreased at 48 hours but still higher than the normal expression.However the expression of RAGE was elevated and peaked at 48 hours(P <0.05).2.The inflammatory response induced by ox-LDL in HUVECs was inhibited by HDL.The levels of HMGB-1,TNF-? and ICAM-1 in the supernatant of the cells and the expressions of HMGB-1 and RAGE protein were decreased with the increase of HDL concentration(P < 0.05).When the concentration of HDL reached 200mg/L,the inhibitory effect on the inflammatory response was the most significant(P < 0.05).3.Compared with the HDL group of healthy subjects,the levels of HMGB-1,TNF-?and ICAM-1 in the supernatant of the cells and the expressions of HMGB-1 and RAGE protein of the HDL group of patients with premature coronary artery disease were increased,but compared with the simulation group,the levels of moleculars above were decreased while compared with the blank group were increased(P < 0.05).Conclusion:1.The HMGB-1/RAGE inflammatory pathway of human umbilical vein endothelial cells can be inhibited by HDL which had anti-inflammatory effects.2.Compared with the HDL group of healthy subjects,the anti-inflammatory effect of the HDL group of patients with premature coronary artery disease was weakened(P<0.05).Its mechanism may be related to its inhibition of the HMGB-1/RAGEinflammatory pathway.It is suggested that the HMGB-1/RAGE inflammatory pathway may be a target for prevention and treatment of premature coronary artery disease.