Vascular endothelium, interacting with blood components, smooth muscle and extracellular matrix, plays a central role in the pathogenesis of inflammation, immunologic reactions, thrombosis, vasospasm, vascular injury and repair, and atherosclerosis. This program project proposes to combine cell biological, immunological, biochemical, morphological and molecular biological approaches, in both in vitro and in vivo models, to gain new insights into the active role of endothelium in these important disease processes. PROJECT 1 will study endothelial-dependent mechanisms of polymorphonuclear leukocyte and monocyte adhesion in vitro and in vivo; PROJECT 2 will examine the effects of disturbed laminar flow on endothelial morphology and function in an in vitro fluid mechanical model; PROJECT 3 will study the expression of endothelial activation antigens and their pathophysiologic consequences in human and baboon vascular tissues; PROJECT 4 will define the nature and mechanisms of action of endothelial-derived factors that influence vascular smooth muscle function; PROJECT 5 will define cellular and molecular mechanisms of endothelial immune accessory functions; PROJECT 6 will study regulation of vascular arachidonic acid metabolism and define novel products in endothelial cells; PROJECT 7 will study the structure, function and expression of endothelial-leukocyte adhesion molecules, using molecular biological approaches; PROJECT 8 will use biochemical and molecular biological approaches (including transgenic mice) to study the structure, regulation and pathobiology of platelet-derived growth factor (PDGF) produced by endothelial cells. CORE A (Cell Culture) will provide well characterized cultures of vascular and nonvascular cells and expertise with co-culture systems; CORE B (Morphology): expertise and facilities for light, scanning and transmission electron microscopy, immunocytochemistry; CORE C (Biochemistry): chromatography (high pressure liquid, gas). UV-spectroscopy capabilities; CORE D (Image Analysis/Computer Support): facilities and professional expertise for biological applications of image analysis technology; CORE E: (Administrative Support).
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