The overall aim of this phased investigator-initiated, multi-center, cooperative study, is to elucidate many of the complex questions concerning the pathogenesis of antherosclerosis. Among the major questions being addressed are: 1) Do all or some fatty streaks progress to fibrous plaques and which are the transitional lesions? 2) What are the morphometric and biochemical lesion changes indicated by progression? 3) What are the frequency and features of insudative and proliferative lesions which may portend progressive disease? 4) What are the qualitative and quantitative effects of risk factors on lesions? 5) What sex differences in lesions account for the paradoxical excess of fatty streaks in young females, even though males develop advanced and clinically manifest disease earlier? This part of the study is concerned with the role of calcium as it relates to some of the above questions. Our working hypothesis is that calcium deposited in the arterial wall enhances the development and progression of the atheroma and may play a role in the transformation of fatty streaks and proliferative lesions into fibrous plaques. The parameters which will be compared with the calcium concentrations are quantitative morphometric measurements of the various lesion types, the amounts of the various lipids, the cellularity of the lesion and its collagen content. In this laboratory we will, in addition to calcium, measure cell proliferation, as indicated by DNA concentration and synthesis, and collagen (the morphometric measurements and the lipid classes will be studied by other Centers). The multi-element nature of the procedure to be used in quantitating calcium, X-ray fluorescence spectroscopy (XRF), will allow us to obtain information regarding trace elements which have been linked to atherogenesis without any additional work or expense.
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