Oxygen radicals alter LDL permeability and uptake by an endothelial-smooth muscle cell bilayer

There is evidence to suggest that the deposition of lipid within the arterial wall, which is characteristic of atherosclerosis, involves a break in the integrity of the endothelial barrier. Oxidative modification of low density lipoproteins by reactive oxygen species may enhance this process. In this study, an aortic endothelial (EC) smooth muscle cell (SMC) bilayer was briefly exposed to a free-radical generating system to determine the effect of superoxides on lipid permeability and uptake. 125I-LDL (10 micrograms/ml) was added to the EC medium at various time intervals (3, 24, and 48 hr and 9 days). The amount of lipid reaching the subendothelial space was measured. Measurements of EC and SMC binding and uptake of LDL were also obtained and compared with those of untreated cells. The results demonstrate a significant increase in the permeability of the treated EC layer to LDL (P less than 10(-6)), which was sustained over time. Superoxide exposure led to a limited initial increase in EC binding and uptake of LDL, which later returned to control values. In contrast, SMC uptake of LDL was significantly (P less than 10(-3)) and persistently increased over control values and disproportionately increased over cellular binding. Such results suggest that superoxides can increase LDL permeability of the EC barrier. Because this was not associated with a comparable increase in EC binding and uptake, it is unlikely to be due to changes in receptor-mediated, transcellular transport.(ABSTRACT TRUNCATED AT 250 WORDS)