Interaction of oxidized low density lipoproteins with both apo B,E and scavenger receptors. A model for its production in vitro.

Oxidation of low density lipoprotein (LDL) has been demonstrated in vivo and directly implicated in the process of foam cell formation. Consequently, a considerable research effort has been devoted to the assessment of the metabolic behaviour of oxidized LDL. We have developed a simple and reproducible model to obtain oxidized LDL consisting of the dialysis of LDL (4 g/l) contained in a cellulose bag against 5 litres of 0.15 M NaCl, 5 microM CuSO4, 0.6 mM FeCl3, pH 7.4, 37 degrees C with constant oxygen bubbling. While the resulting particles have a number of physicochemical properties suggesting lipid oxidation, neither apo B fragmentation nor modification in the size and shape were observed. This oxidized LDL showed internalization into cells through both the apo B,E and the scavenger receptors and the rate of removal from the plasma in injected rats was faster than that observed for normal LDL. We suggest that these particles may represent an equivalent to the circulating oxidized LDL postulated in humans.