Local intimal-medial uptakes of 125I-albumin, 125I-LDL, and parenteral Evans blue dye protein complex along the aortas of normocholesterolemic minipigs as predictors of subsequent hypercholesterolemic atherogenesis.

Abstract

[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" 1 ). We conclude that (1) transport of albumin and LDL across the intact, normocholesterolemic, aortic endothelial surface is independent of pressure;

Arterial Hypertension, Microalbuminuria, and Risk of Ischemic Heart Disease

“…[43][44][45][46] In animal models, it has been shown that the transvascular leakage of albumin and lipoproteins are tightly correlated 47,48 and that both are elevated in atherosclerosis 49 and in atherosclerosis-prone sites of arteries. 50 …”

Site Specificity of Atherosclerosis

“…23 Albumin-bound Evans blue dye, radioactive albumin, radioactive fibrinogen, horseradish peroxidase, and radioactive LDL have all been shown to localize to areas of increased permeability and increased atherosclerosis susceptibility. 24 In general, there is a gradient of aortic permeability to LDL in a cephalic to caudal direction, and this is mirrored by cholesterol accumulation in the aorta of cholesterol-fed rabbits. 25 At the rabbit aortoiliac bifurcation, LDL incorporation is greater along the lateral wall, with lower shear force and higher susceptibility for atherosclerosis than along the medial wall.…”

Laminar Shear Stress

“…Other investigators have confirmed these findings in different areas of the vasculature for both rabbits 48 and pigs. 49 Mechanistically, it appears that compromised endothelial cell integrity, and hence increased macromolecule permeability, results from high shear gradients that are present in low shear stress/flow reversal conditions (See Weinbaum and Chien 50 for review). A study by Sprague et al 51 showed that 125 I-LDL internalization increased in bovine aortic endothelial cells exposed to steady stress conditions for 24 hours; however, this likely reflects an increased metabolic need for LDL under steady shear conditions rather than increased LDL incorporation into the arterial wall.…”