Atherogenesis may be associated with increased transport of low density lipoproteins (LDL) into the arterial wall; and normal transport rates may be enhanced by mechanical, chemical, or immunological injury to the endothelium. The objectives of the proposed research include determinations of a) how rapidly LDL (and perhaps other proteins) enters the arterial wall, b) the extent to which perturbations from the normal state, particularly endothelial injury, influence LDL transport, and c) the transport mechanisms which may be important and the magnitude of the transport parameters. We plan to measure aortic transmural concentration profiles and total uptake of radioiodinated LDL and albumin at specific times following injection into rabbits using both serial frozen microtomy and autoradiography in order to assess concentration levels. These experiments will be carried out in normal controls and in studies designed to determine the effects of various interventions upon LDL transport and accumulation. Interventions will be directed largely at those processes which are thought to affect the endothelium.
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