IRON OVERLOAD AUGMENTS THE DEVELOPMENT OF ATHEROSCLEROTIC LESIONS IN RABBITS

Iron, a major oxidant in vivo, could be involved in atherosclerosis th rough the induction of the formation of oxidized LDL, a major atheroge nic factor. This study was designed to test this hypothesis experiment ally. Four groups of New Zealand White rabbits were included: iron-ove rloaded/hypercholesterolemic (group A, n=8), iron-overloaded (group B, n=6), hypercholesterolemic (group C, n=6), and untreated (group D, n= 6). Iron overload was achieved by the intramuscular administration of 1.5 g of iron dextran divided in 30 doses. Hypercholesterolemia was pr oduced by feeding rabbit chow enriched with 0.5% (wt/wt) cholesterol. Serum iron, ferritin, cholesterol, triglycerides, and lipoperoxides in serum were measured throughout the study. Lipoperoxides were measured at the end of the study in liver, aorta, and spleen homogenates. Aort as of groups A and C had multiple lesions; however, group A had greate r lesional involvement than group C (P<.05). Lesions were not observed in rabbits fed normal chow (group D). As expected, serum iron and fer ritin were above normal levels in groups A and B. Serum cholesterol in creased in groups A and C. Lipoperoxides in liver and spleen homogenat es of iron-overloaded rabbits were increased. Interestingly, iron depo sits were seen by ultrastructural studies in the arterial walls of rab bits in groups A and B. Our study suggests that iron overload augments the formation of atherosclerotic lesions in hypercholesterolemic rabb its.