This research aims to characterize and correlate morphologic, biochemical and hemodynamic changes in atherosclerotic plaques during development and regression of atherosclerosis in non-human primates. Specific aims are to determine: 1. If fatty streaks progress to fibrous plaques and, if so show this occurs morphologically and biochemically. Sequential changes in mass of lipids, collagen and elastin at sites of plaque progression will be measured along with long-term turnover of collagen and elastin. 2. The effect of regression on changes observed during progression and susceptibility of plaques to regression induced by various means of therapy to control lipids or connective tissue responses. The characteristics of early and intermediate lesions which indicate their course of development. To accomplish these aims, techniques developed in these laboratories for direct sequential observation and sampling of plaques during development of atherosclerosis will be extended. The use of animals whose collagen and elastin have been made chronically radioactive with 3H-proline will permit simultaneous determinations of turnover in new and old collagen and elastin in response to progression and regression of atherosclerosis. These changes will be correlated with morphology of the plaque and encroachment into the vascular lumen observed surgically and angiographically. The effects of modest sustained hyperlipidemias in non-human primates comparable to those occurring in man will be emphasized. Ultimately, this research promises an understanding of sequential changes in atherosclerotic plaques in the non-human primate; this information will provide a better framework for understanding this disease in man. BIBLIOGRAPHIC REFERENCES: Klein, L., DePalma, R.G., Insull, W. Jr., Koletsky, S., and Bellon, E.M.: Stability of original collagen and elastin and gain of new collagen in atherosclerotic plaques. American Society for the Study of Arteriosclerosis, p. 23, Nov. 1976 (Abstract). DePalma, R.G., Koletsky, S., Bellon, E.M., and Insull, W. Jr.: Failure of regression of atherosclerosis in dogs with moderate cholesterolemia. Atherosclerosis 1977, in press.
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