Local Intimal-Medial Uptakes of I-Albumin, I-LDL, and Parenteral Evans Blue Dye Protein Complex Along the Aortas of Normocholesterolemic Minipigs as Predictors of Subsequent Hypercholesterolemic Atherogenesis

This report describes the normalized intimal-medial uptakes [uptake {M, mg • cm~)-r-serum concentration (c0, mg • cm" )] of I-albumin, I-low-density lipoprotein (LDL), and in vivo Evans blue dye (EBD)-albumin complex as functions of pressure (P), time (t), molecular species (i), and location (z) along a ventral longitudinal z axis of the normal, intact, aortic endothelial surface in adult normocholesterolemic Sinclair Research Farm (SRF) minipigs and compares these uptake (A//c0) measurements with atherogenesis in hypercholesterolemic cohorts. Uptakes of porcine serum I-albumin (n=21) and I-LDL (n=10) were measured in freshly excised, metabolically supported aortas using a recently developed organ-support system. In vivo intimal-medial EBD uptake vs z data were measured photometrically on opened descending aortas from another group (n=6) of normocholesterolemic, adult, SRF minipigs 18 hours after the intravenous administration of EBD. For comparison purposes, the corresponding incidence of atherosclerotic lesions along the aortic z axis was calculated using topographic data from hypercholesterolemic minipig cohorts (n=39). The results showed that uptakes varied greatly with t, z, and macromolecule (i) but not with P. More specifically, the value of Af/c0 at any location (z) rose with t, was insensitive to P, decreased with macromolecular (i) size, and varied with z in a pattern that "peaked" in the upstream region, decreased to a nadir in the downstream region, and then rose again as it approached the abdominal celiac orifice. The spatially z-averaged uptake rates for the three different labeled serum proteins were 0.31x10"' cm • IT for I-albumin, 0.42x10"' cm • h" for EBD-albumin, and 0.04x10"' cm • h" for I-LDL. Nondimensionalized analysis of the individual sets of uptake data indicated that the overall uptake relationship [A/(t,P,z,<)/c,o, cm] could be characterized empirically by the simple product of two separate functions: one, a "scaling function" [m(z,i)], that described the uptake magnitude for a given i and z and appeared to be independent of t or P; the other, a "shape function" O(t,P)], that described the shapes of the uptake vs t and P relationships and appeared to be independent of z or i. The "scaling function" [m(z,i)] vs z contour appeared to correlate well with the corresponding atherosclerotic lesion incidence vs z contour from the group of hypercholesterolemic minipig cohorts. Assuming passive transport, it was shown ("Appendix") that m(z,i) can be interpreted physically in terms of an endothelial diffusive permeability coefficient (9\ cm • s"). We conclude that (1) transport of albumin and LDL across the intact, normocholesterolemic, aortic endothelial surface is independent of pressure;