Correlation of iron and zinc levels with lesion depth in newly formed atherosclerotic lesions

Several studies have indicated a relationship between body iron content and cardiovascular disease, although other studies have not. There are also suggestions that zinc has an antioxidant and antiatherosclerotic effect. We have used Nuclear Microscopy, using the combination of Scanning Transmission Ion Microscopy (STIM), Rutherford Backscattering Spectrometry (RBS), and Proton Induced X-ray Emission (PIXE) to map and quantify iron and zinc levels in newly formed atherosclerotic lesions. Sixteen New Zealand White rabbits fed on a high cholesterol diet were divided into four groups of 4 rabbits each. Six weeks into the high cholesterol diet, two groups were treated with the iron chelating agent desferrioxamine, for 2 weeks and 4 weeks, respectively, by surgically implanting with Alzet osmotic pumps (Alza Corporation, Palo Alto, CA, USA) containing desferal (0.5 g/ml). The other two groups served as controls, and were surgically implanted with osmotic pumps containing saline. Tissue sections were taken from the aortic arch, flash frozen, and air-dried. Analysis of atherosclerotic lesions indicated a trend (p =.07) to a reduction in the progression of the lesion after 4 weeks of desferrioxamine treatment. For each of the control and desferrioxamine-treated animals however, the more extensive lesions contained a higher concentration of iron and a lower concentration of zinc. Our results are consistent with the view that early lesion formation may be accelerated by free radical production caused by increased iron levels, that zinc might antagonize such effects, and that more prolonged desferal treatment might have an antiatherosclerotic effect.