Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins.

We have investigated whether and how the elevated glucose concentrations characteristic of diabetes may alter the interaction of endothelial cells with low-density lipoproteins (LDL). Protracted exposure of cultured human endothelial cells to 20 mmol/l glucose failed to affect either the relationship between the degree of confluency of the monolayer and the extent of LDL degradation or the dose-responses for LDL uptake and degradation. In contrast, non-enzymatic glycosylation of LDL by pre-incubation of LDL with glucose markedly inhibited their uptake and degradation by endothelial cells. Thus, at protein concentration of 5 micrograms/ml, the amount of glycosylated 125I-LDL associated with cells was decreased fourfold compared with native 125I-LDL (47 +/- 3 versus 194 +/- 10 ng X mg cell protein-1 X 24 h-1, mean +/- SEM), and degradation was decreased twenty-fold (135 +/- 4 versus 2873 +/- 115 ng X mg cell protein-1 X 24 h-1). The degree of inhibition was proportional to the extent of glycosylation. At all concentrations studied, methylated LDL behaved similarly to glycosylated LDL. The decreased recognition of glycosylated LDL by the endothelial lining of small and large blood vessels may have an impact of tissue physiology and on the overall fate of the glycosylated molecules.