Oxidized Lipoproteins Degrade the Endothelial Surface Layer

Abstract

Background —Flowing erythrocytes and platelets are separated from the luminal endothelial cell (EC) surface by a 0.5-μm-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 CuSO 4 for 6 hours. The dimension of the EC surface layer averaged 0.6±0.1 μm 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.