The material for these studies will be derived from the PDAY research program, a unique multicenter research effort which involves the collection of samples of coronary arteries, aortas, and other designated small blood and tissue samples from young persons. The study population is individuals 15-34 years of age who are free from underlying chronic disease and who for the most part die suddenly and unexpectedly from trauma and who are autopsied as a part of a forensic investigation. These special studies will not only involve cases collected during phase 2 of the study (1987-1990), but will utilize samples from cases now being collected to include more adequate numbers of females, more raised atheromatous lesions, and more samples for hepatic apolipoprotien DNA analysis. Previous studies from PDAY have determined that certain areas in human arteries have a high probability of forming atherosclerotic lesions, whereas, immediately adjacent sites are spared. Published results from this laboratory have demonstrated similar areas in the swine model. These lesion-susceptible (S) regions demonstrate altered endothelial cell morphology and function even in normal animals, with further alterations induced by hyperlipemia. These studies have also shown that one of the earliest cellular events in the atherogenic sequence in animal models is the preferential recruitment of blood monocytes into S-regions, a mechanism apparently controlled by production of specific chemotactic factors in these areas. However, alteration of endothelial cell structure and function have not been demonstrated in S-regions of human arteries, and although monocytes and other leukocytes has been demonstrated in human lesions, the relationships between altered endothelial structure, S-regions and monocyte recruitment in human atherogenesis remains unclear. The overall objectives of the proposed studies are to determine if alterations in endothelial cell structure and function exist in S-regions in human; to ascertain whether such alterations are associated with adherence and intimal accumulations of monocytes; and to determine if S-region endothelium and/or intima cells produce factors controlling monocyte production and recruitment.
