A nuclear microscopy study of trace elements Ca, Fe, Zn and Cu in atherosclerosis

Abstract

Quantitative mapping of trace elements Ca, Fe, Zn and Cu can be achieved in biological tissue using a nuclear microprobe. Presented here is a brief review of the work we have carried out in the last decade using the nuclear microscope to try and elucidate the role of trace elements Fe, Zn, Cu and Ca in induced atherosclerosis in New Zealand White rabbits fed on a 1% cholesterol diet. The lesions were studied using nuclear microscopy, incorporating a combination of ion beam techniques: particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and scanning transmission ion microscopy (STIM). Iron is present in early lesions at concentrations around seven times higher than the artery wall. Measurements of localized lesion iron concentrations were observed to be highly correlated with the depth of the lesion in the artery wall for each individual animal, implying that local elevated concentrations may provide an accelerated process of atherosclerosis in specific regions of the artery. When the rabbits were kept mildly anaemic, thereby reducing iron levels in the lesion, the progression of the disease was significantly slowed. Iron chelation using desferal showed that early treatment (three weeks into the high fat diet) for relatively long periods (nine weeks) significantly retarded the progression of the disease. Zinc is depleted in the lesion and is also observed to be anti-correlated with local lesion development and feeding the rabbits on a high fat diet with zinc supplements inhibited lesion development, although since no significant increase in lesion zinc levels was measured, this anti-atherosclerotic effect may be indirect. Copper, measured at low levels (∼3 ppm) in the early lesion, is also depleted compared to the artery wall, suggesting that it is not a major factor in atherogenesis. Calcium is also depleted in early lesions, although at a later stage mineral deposition (hydroxyapatite) is observed to take place in the lesion/artery wall interface (intima), and subsequently in the lesion. These results are consistent with the hypotheses that iron plays a role in atherosclerosis probably through the production of free radicals and that zinc has an indirect protective effect. Copper appears to have a minor role due to its low lesion concentrations and hydroxyapatite deposition is a relatively late event. © 2006.