The specific aim of this project is to characterize the structural and physical processes that participate in the metabolic balance of arterial walls by applying the principles of bionengineering and mass transport. The long-term objective is to gain new knowledge relevant to the in situ physical-chemical mechanisms and underlying structural features responsible for the intimal accumulations of atherosclerosis. The transmural transport of ferritin and of radiolabeled (Idodine 125) albumin, HDL, and LDL across the intact and de-endothelialized intimal surfaces of adult minipig arteries and veins will be studied in a specifally designed in vitro system. This system permits discrete experimental control of pertinent variable such as local chemical milieu, pressure, wall stretch, etc., at 12 contiguous sites along the length of the vessel. The uptake (M nmol cm-2) and the transmural concentration distribution (c(chi) nmol cm-3) of the labeled protein will be measured as a function of duration (T) of exposure, transmural pressure (P), wall strain (S), endothelial damage, temperature, and local chemical milieu. The c(chi) will be calculated from microdensitrometric measurements of silver distribution across microautogradiographic preparations. The c(chi) data will be correlated with structural detail from adjacent light and electron micrographs (SEM and TEM). The three main classes of blood vessels, vein (jugular), elastic artery (thoracic aorta), and muscular artery(cartoid or ilio-femoral0, will be studied in the above manner from each of the following: normal adult equal 24 mo), aged (equal 12yr), balloon-injured, and hypercholesterolemic minipigs. The c(chi) data from these vessels will fitted to tentative mathematical models to obtain numerical estimates of the parameters describing the underlying physical and chemical process. With this information, we may begin to understand 1) the mechanisms by which certain sites in the vascular tree are essentially unaffected by atherosclerosis, while others characteristically progress to the atheromatous plaque, 2) how to design rational strategies for prevention and therapy of vascular disease, and 3) how to develop enduring surgical replacement procedures.
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