Effects Of Irbesartan On Expression Of Lectin-like Oxidized Low-density Lipoprotein Receptor-1in Cultured Thp-1Cells

BackgroundAtherosclerosis is the main cause of cardiovascular disease, which influences human body health.As people living standard rise, cardiovascular diseases have been increasing.Foam cells play a critical role in the development of atherosclerosis, which are formed by Macrophages intaking oxidized low density lipoprotein through scavenger receptors.Lectin-like oxidized low-density lipoprotein receptor-1is a kind of scavenger receptors,which was discovered in1997.LOX-1is expressed not only in endothelial cells, but also in macrophages,vascular smooth muscle cells and platelets.It plays an important role in the development of atherosclerosis.Diabete is an important risk factor of atherosclerosis,the incidence and mortality of cardiovascular disease increase during diatetes.Irbesartan is angiotensin II receptor blocker, some researches have found that early treatment with ARB may prevent diabetic microangiopathy. Other studies have found that ARB drugs may slow down or reverse atherosclerosis through various ways. Whether Irbesartan can markedly decreased high glucose-induced LOX-1mRNA and protein expression or not,currently there is no reports.ObjectiveTo investigate the influence of glucose and irbesartan on expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) mRNA and protein in cultured THP-1cellsMethodsTHP-1cells were differentiated by incubation with160nM PMA for72hours.The cells were divided into three groups:control group, glucose group (5mmol/L、8mmol/L、12mmol/L、15mmol/L),irbesartan intervention group (1μmol/L、0.1μmol/L、0.01μmol/L).Then the cells in glucose group were incubated with several concentrations glucose for24hours. The intervention group was first treated with irbesartan for2h,then co-incubated with high glucose for24h.Real time PCR and enzyme-linked immunosorbent assay technology were used to detect LOX-1mRNA and protein expression.Results(1) THP-1cells are differentiated into macrophages after72h of PMA treatment.(2) Compared with control group,the expression of LOX-1mRNA and protein showed no significance in5mmol/L glucose group(P>0.05),but the expression in high glucose groups increased significantly (P<0.01),and the increase was dependent on glucose concentration.(3) Compared with15mmol/L glucose group, Irbesartan group markedly decreased high glucose-induced LOX-1mRNA and protein expression, the expression during irbesartan intervention group showed significantly (P<0.01), and the decrease was dependent on irbesartan concentration.ConclusionHigh glucose can upregulate LOX-1mRNA and protein expression in a concentration-dependent manner and may contribute to the pathogenesis of atherosclerosis.Irbesartan can block the effect of high glucose and may produce anti-atherosclerosis.