Oxidized lipoproteins degrade the endothelial surface layer - Implications for platelet-endothelial cell adhesion

[摘要] Background-Flowing erythrocytes and platelets are separated from the luminal endothelial cell (EC) surface by a 0.5-mu m-wide space named the endothelial surface layer. We hypothesized that the disruption of the endothelial surface layer by oxidized low-density lipoproteins (Ox-LDL) contributes to atherogenic increases in vascular wall adhesiveness. Methods and Results-The hamster cremaster muscle preparation was used for intravital microscopic observation of the distance between erythrocytes and the capillary EC surface. Moderate Ox-LDL was prepared by exposing native LDL to CuSO4 for 6 hours. The dimension of the EC surface layer averaged 0.6+/-0.1 mu m during control situations, but a bolus intravenous injection of Ox-LDL (0.4 mg/100 g of body weight) transiently diminished the EC surface layer by 60% within 25 minutes, which correlated with a transient increase in the number of platelet-EC adhesions. Combined administration of superoxide dismutase and catalase completely blocked the effect of Ox-LDL on the dimension of the EC surface layer and inhibited platelet-EC adhesion. Conclusions-Oxygen-derived free radicals mediate the disruption of the EC surface layer and increase vascular wall adhesiveness by Ox-LDL.

[关键词] GLYCOCALYX;VASOCONSTRICTION;PERMEABILITY;CAPILLARIES;ALBUMIN;FLOW;LDL