Glycoxidized LDL increases lectin-like oxidized low density lipoprotein receptor-1 in diabetes mellitus

Abstract

Aims LDL is subjected to glycoxidation in diabetes mellitus. We have evaluated the effect of glycoxidized LDL on lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in endothelial cells in vitro, as well as the relationship between glycoxidzied LDL and LOX-1 in type 2 diabetic patients with and without microalbuminuria in vivo. Methods Endothelial cells were incubated with modified LDL including glycoxidized LDL, oxidized LDL (oxLDL), glycated LDL, and acetylated LDL, and cellular LOX-1 and the soluble forms of LOX-1 (sLOX-1) in cell medium was measured. Glycoxidized LDL in diabetic patients was determined by measuring the glycoxidation product N ɛ-(carboxymethyl)lysine (CML) in apolipoprotein (apo) B. Serum oxLDL and sLOX-1 was determined by ELISA. Results Only glycoxidized LDL and oxLDL significantly increased LOX-1 expression ( p < 0.05) and the production of sLOX-1 ( p < 0.05), and the effect of glycoxidized LDL was greater than that of oxLDL. Both normoalbuminuric ( n = 110) and microalbuminuric ( n = 91) patients had higher serum apoB-CML than controls ( n = 105) ( p < 0.01), but oxLDL was only elevated in the microalbuminuric patients ( p < 0.05). Serum sLOX-1 was significantly increased in both groups of patients compared to controls ( p < 0.01). Serum sLOX-1 correlated with apoB-CML ( r = 0.36, p < 0.001) but not with oxLDL. The relationship between sLOX-1 and apoB-CML was independent of HbA1c, age, gender, BMI and smoking status. Conclusion Glycoxidized LDL was more potent than oxLDL in inducing LOX-1 in vitro. Serum concentration of apoB-CML, a marker of glycoxidized LDL, was increased in type 2 diabetic patients with and without microalbuminuria, and this was associated with an increase in serum sLOX-1.