This proposal contains three separate projects from the Medical College of Georgia as part of an investigation initiated multi-center study of pathobiological determinants of atherosclerosis in youth. The long-term objective of this multi-center study is to define more precisely the pathogenesis of human atherosclerosis during the age period of 15-34 years and also to determine if selected risk factors for clinically manifest coronary heart disease in middle age influence the process of atherosclerosis during this age period. The material for the study will be derived from autopsies performed in about 15 centers across the United States of America on disease-free subjects in this age group dying suddenly or from accidents, mostly from vehicular accidents. The material collected will include the aorta and coronary arteries, other tissues and blood and relevant personal data. A multi-pronged approach, utilizing traditional morphological and chemical techniques as well as more sophisticated methodologies, will attempt to answer several specific questions, some of which are outlined below. Do lesions characteristic of later childhood (fatty streaks) evolve into lesions that, in adulthood, are closely associated with arterial occlusion and ischemia (fibrous plaques) If such progression did seem to occur, what are the earliest detectable changes indicative of progression in the fatty streak? Are there differences in regard to the occurrence of microthrombi, collagen composition of the intima, endothelial covering, number, types and qualities of cells populating the intima and trace element and chemical composition? Are there lesions other than fatty streaks that may be precursors of the fibrous plaques? This proposal includes (1) details of collection of specimens from autopsies performed in three hospitals in the Augusta area, (2) a histochemical and histological study of the collagen characteristics of the intima and media and the relationship of the collagen composition to intimal thickness, presence of unesterified cholesterol, neutral fat, smooth muscle proliferation, atheronecrosis and other lesions of intima and media and (3) a scanning electron microscopic study to determine the frequency and characteristics of microthrombi in selected sites of the coronary arterial system and the aorta.
