As a portion of a phased (1,2, and 3) investigator initiated, multicenter, cooperative study aimed at major questions concerning the pathogenesis of atherosclerosis, this segment of the interinstitutional study is guided by the overall purpose of the entire project and by the major questions being addressed in the project. As in other centers, autopsy tissue from young accident victims will be studied using the standard multicenter protocol. At the University of Nebraska Medical Center people age 5 through 35 years of age will be included. Sepcific aims include 1) quantitative characterization of cell types within fatty streaks and fibrous plaques in aorta and coronary arteries by immunocytochemical techniques identifying lymphocyte populations, monocytes and macrophages, smooth muscle cells and endothelial cell antibodies, 2) using these quantitative identification methods to distinguish the evolutionary course of different fatty streaks, insudative and proliferative lesions, and fibrous plaques, 3) characterization of the inflammatory cell populations in adventitia of aorta and coronary arteries, 4) establishment of the origin of foam cells within fatty streaks or within evolving fibrous atherosclerotic plaques; in other words, the immunohistochemical techniques will allow differentiation of cells of smooth muscle and circulating blood monocyte origin. A quantitative differential will be made between the different types of intimal lesions, 5) correlation of inflammatory populations will be correlated with corresponding observations on immune complex deposition, viral genome and other indicators of inflammatory/infectious/immunological etiologies of atherosclerosis, 6) determination of collagenase and elastase activity, complementary to the quantitative determination of total collagen and collagen types within the plaques and aortic and coronary walls, and 7) quantitation of mucopolysaccharide fractions in the same tissues. The quantitative biochemical studies will be conducted in correlative comparison with other connective tissue characterization being done at other centers in this investigation.
