Nuclear microscopy of atherosclerotic tissue: A review

This paper reviews the work carried out in the Research Centre for Nuclear Microscopy, NUS on the role of iron in coronary heart disease, using the te chnique of nuclear microscopy to determine the levels of iron and other tra ce elements in the artery wall and lesions. These investigations have indic ated that iron may play a significant role in the development of atheroscle rosis, probably through the promotion of cytotoxic free radicals leading to the oxidation of low-density lipoprotein (LDL). Using a rabbit model we ha ve observed that early atherosclerotic lesions, induced by feeding the anim als on a 1% cholesterol diet, contain increased levels of iron (up to 8 tim es) compared with the adjacent healthy artery wall. In a follow-up time seq uence study, we have shown that iron accumulation occurs at the onset of le sion formation, which takes place around 4-6 weeks after exposure to the 1% cholesterol diet. As the lesions mature, they enlarge to occupy a signific ant fraction of the artery wall, and at about 16 weeks the lesions begin to show signs of calcification. In an additional experiment, where the choles terol fed rabbits were kept anaemic through weekly bleeding, the iron conte nt of the artery wall was reduced and the onset of atherogenesis was delaye d. In a further investigation, rabbits were fed on a 1% cholesterol diet an d after 6 weeks (corresponding to the period of early lesion formation) a t est group was subjected to treatment using the iron chelator desferal. Prel iminary results indicate that during the treatment with desferal, lesion de velopment was slowed down. (C) 2001 Elsevier Science BN. All rights reserve d.