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

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.

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(epsilon)-(carboxymethyl)lysine (CML) in apolipoprotein (apo) B. Serum oxLDL and sLOX-1 was determined by ELISA.

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.

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.