Oxidation decreases low density lipoprotein association with the subendothelium extracellular matrix

Atherosclerosis is initiated by accumulation of low density lipoprotein (LDL) in the subendothelium extracellular matrix (ECM) followed by oxidation and scavenger receptor mediated uptake by the vessel wall recruited macrophages. The effect of oxidation on LDL association with the ECM is not yet clear. In the present study we examined the hypothesis that excessive oxidation of LDL results in decreased LDL association with ECM, thereby increasing its accessibility to the scavenger receptor on macrophages. We have studied the relative association of Cu⁺² ion oxidized LDL to native LDL with the native or oxidized bovine corneal endothelial cells ECM. Oxidation of LDL decreased its binding to the ECM. The kinetic of this process was characterized by approximately 1 h lag phase followed by a significant decreased binding of 80% after 6.5 h oxidation. This kinetic more closely resembled the pattern of the oxidation product dienals accumulation rather than thiobarbituric acid reactive substance formation. Oxidation of ECM-bound LDL resulted in an increased LDL release from the ECM as a function of Cu⁺² concentration with a maximal increase of 2-fold at 3 μM. ECM oxidation prior to exposure to LDL resulted in a 30% decrease in LDL binding to the ECM. In conclusion, these results suggest that oxidation processes in the vessel wall result in increased dissociation of ECM-bound LDL, which in turn makes this oxidized LDL more accessible for binding and uptake by macrophages leading to foam cell formation.