This proposal represents an application by the University of Maryland for its participation as 1.) Collection Center and 2.) Study Center in a multi-center collaborative study on the """"""""Pathological Determinants of Atherosclerosis in Youth"""""""". The multicenter study focuses on early atherosclerotic lesions in a young adult population of both sexes aged 15 to 34. Information is sought on nascent stages of antherosclerotic lesions in the aorta and coronary arteries and on the role of risk factors. 1.) According to the plan the Universiy of Maryland will rapidly collect fresh aortas and coronary arteries from disease free victims of violent death and mail these to Louisiana State Medical Center, acting as the collection center. From there portions of the tissue are sent to the participating study centers. Biographical data will be forwarded to University of Texas Health Center in San Antonio acting as Statistical Center. The overall management will rely on the Administration and Sample Coordinating Center located at the University of Chicago under Dr. Wissler. 2.) The Study Center at the University of Maryland will focus on the endothelial and intimal lesions. Under the hypothesis that intimal injury initiates early atherogenesis we intend to describe the circumstances of such early reactions. The University of Maryland is well suited for this task because of the establishment of the Immediate Autopsy Program (IA) that provides specimens virtually free of autolysis. The IA program will permit endothelial alteration to be reviewed by Scanning and Transmission Electron Microscopy, the identification and quantitation of the distribution of Apolipoproteins in the intima, the assessment of the presence and location of platelet antigens and fibrinogen in intimal lesions and characterization of the proliferating smooth muscle cells for their cellular filaments. Such characterization will also be extended to inflammatory cells in particular macrophages present in the intima. X-ray microanalysis on rapidly collected samples can illustrate the presence and role of calcium in degenerating cells and extracellular precipitates. Tissue samples will also be screened for the presence of choleserol oxides a component that has been shown to be injurious to intimal cells. Collaborative efforts are planned with the University of Chicago, Albany Medical College and University of Washington. The overall integration into the multi-center study allows this program an unusual depth.
