The effect of Glycoxidized Ldl on Monocytes/ Macrophages Cell Line (THP-1) Gene Expression

Abstract

Introduction: Cardiovascular complications are the leading cause of morbidity and morality in patients with diabetes mellitus. Epidemiological studies have shown that hyperglycemia and dylipidemia are two risk factors for diabetic atherosclerosis. Lipoprotein is subjected to both glycation and oxidation in diabetes. The biological effects of glycoxidized LDL have not been well characterized. The objective of this study is to investigate whether glycoxidized LDL induce the gene expression of human monocyte/macrophages, using the THP-1 cell line, by modified lipoprotein. Methods: Glycoxidized LDL was obtaining by incubating LDL with glucose and copper ion for 7 days. The extent of oxidation was measured by TBARS assay. Monocytes/ macrophages cell (THP-1) was incubated with glycoxidized LDL for one day. The gene expressions were quantified using quantative PCR. Results: The oxidation of glycoxidized LDL was significantly higher than native LDL (7.12+2.7 nmol MDA/mg protein versus 1.615+0.459 nmol MDA/mg protein). The gene expression of CD36 has been upregulated by 4.6+1.09 folds when incubated with glycoxidized LDL at 100ug/ml. The gene expression of SR-BI was suppressed by glycoxidized LDL by 4.8+1.64 folds. Conclusion: Glycoxidized LDL regulate the gene expression of CD36 which may increase the binding and internalization of modified LDLs by macrophages. Down regulation of SR-BI may lead to a decrease in cholesterol efflux. These gene expression profiles have suggested some potential mechanisms for the contribution of modified LDL to the development of diabetic atherosclerosis.