Atherogenic modified LDL in diabetes

This paper summarizes the recent findings on LDL atherogenic modifications in diabetic patients. LDL from diabetic patients, unlike LDL from healthy subjects, caused a significant increase in cholesterol content of cells cultured hom unaffected human aortic intima, i.e., produced a direct atherogenic effect. LDL was divided into two fractions (nonbound and bound) by affinity chromatography on Ricinus communis agglutinin-agarose. The amount of bound LDL was significantly higher in diabetic patients compared with healthy subjects. Bound LDL was characterized by significantly lowered sialic acid content and a significantly increased fructosyl lysine level compared with unbound LDL, i.e., was desialylated and nonenzymatically glycosylated lipoprotein. The bound (desialylated), but not unbound (sialylated), EDL subfraction induced cholesterol accumulation in cultured cells. Bound LDL was also characterized by a significantly lowered content of neutral lipids and demonstrated increased electrophoretic mobility on agarose gel electrophoresis. Bound and nonbound LDL differed significantly in hydrated density and particle size, as was determined by density gradient ultracentrifugation and native polyacrylamide gradient gel electrophoresis. The results of this study have shown that the in vivo modified atherogenic LDL subfraction in the blood of diabetic patients is represented by small, dense, more electronegative, desialylated, and glycated LDL.