Ceruloplasmin and oxidized LDL colocalize in atherosclerotic lesions of hamster

Epidemiological studies show that the risk for cardiovascular diseases increases with increasing levels of free-copper in plasma. It is known that intact ceruloplasmin (CP), the major protein transporter of copper in human plasma, oxidizes low density lipoproteins (LDL) in vitro. Our aim was to study the interaction between LDL and CP in vitro and in vivo, in an animal model of diet-induced atherosclerosis. In order to visualize the pathway of LDL into the arterial wall, human native LDL was labeled with fluorescent DiI and injected into male, Golden Syrian hyperlipemic hamsters. In vitro results demonstrated that slightly degraded CP has a significant oxidation potential against LDL at neutral pH. In vivo, after 24 hours circulation, LDL-DiI was taken up by the enlarged intima and fatty streaks of the arterial wall. Immunohistochemical localization of oxidized LDL and CP revealed their presence in the same areas of the arteries that take up LDL-DiI. Co-localization of LDL and CP in the enlarged intima of pro-atherosclerotic areas might explain the possible copper-induced oxidation process that might occur after native LDL is taken-up from the blood, transcytosed through the endothelium and accumulated in focalized deposits.