PATHOBIOLOGICAL DETERMINANTS OF ATHEROSCLEROSIS IN YOUTH

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.