The proposed project concerns two main lines of investigation: (1) continuation of cell biology studies by the investigation especially of the biochemical organization of normal endothelium. The inquiries will include: (a) surface chemistry of microvascular endothelium in special capillary beds such as those of the lung, liver, muscle; possible local modulations of microdomains in arterioles, capillaries and venules will be also surveyed; (b) mapping of surface chemistry and membrane chemistry of endothelium in those vascular segments most frequently affected by atherosclerosis and thrombosis (coronary, cerebral, aorta, endocardium); (c) identification of mechanisms involved in electrostatic sorting and gatting of macromolecules by vascular endothelium; (d) continuation of the work for isolation of a membrane fraction from microvascular endothelium (rabbit myocardium) and arterial endothelium (bovine aorta). (2) Studies of experimental cell pathology by the search for mechanisms by which abnormal conditions can modify the chemistry of endothelial surface, and subsequently its reactivity and permeability, thus facilitating or inducing atherosclerosis and thrombosis. The investigations will include: (a) extension of the survey on the vessels mentioned under (1b) as a function of aging and hypercholesterolemia; (b) survey of the rate of transport of intact or modified LDL across the endothelium of large and small vessels in normal and abnormal conditions; (c) chemistry of platelet surface and membrane (especially endogenous lectins) in relation to platelet interactions with endothelium. The final goal is to identify the biochemical factors and mechanisms which may be involved in the prelesion stage of atherosclerosis and thrombosis.
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