This A/SCOR will continue to employ a multidisciplinary approach to elucidate factors involved in the pathogenesis of atherosclerosis. Studies will be carried out in the areas of lipid biochemistry and enzymology, diet-induced primate atherogenesis, hemodynamics, platelet-endothelial interactions, endothelial injury and repair, prostaglandins, lysosomal enzymes, and the atherogenic risk factors in a pediatric population. One of the unique features of this program is the strong emphasis on endothelium as it relates to the progression and complications of atherogenesis. In this regard, cultured umbilical vein, arterial and brain capillary endothelium are available on a continuing basis for biochemical immunologic and morphologic study. A major goal is to relate lipid risk factors to thromboatherogenic mechanisms. Another asset is the availability of nonhuman primates in which to investigate the progression and regression of atherosclerosis and hemodynamic changes associated with these processes. A third unique feature is the availability of a large, well-characterized pediatric population for epidemiologic and genetic studies. Our program consists of eight research projects and five supporting core units. The projects deal with the cellular and membrane aspects of fatty acid saturation; lipid, permeability and morphologic changes in the arterial wall of the primate; hemodynamic changes during progression and regression of atherosclerosis; the role of prostacyclin, hydroxyeicosatetraenoic acids, and protein phosphorylation in endothelial function; the properties of cerebrovascular endothelium, and recognition, uptake and function of lysosomal acid lipase; and finally, the incidence, prevalence and tracking of hyperlipidemia, hypertension and obesity in a school age population, with emphasis on the familial aspects of lipoprotein and hemodynamic abnormalities.
