Uptake of low density lipoprotein, albumin, and water by deendothelialized in vitro minipig aorta.

Abstract

The purpose of this research was to study the effect of pressure on arterial hydration in vitro and the effect of pressure and flow (stirred reagent) on the in vitro transport of 125I-albumin and 125I-LDL into deendothelialized minipig aortas over a 24-hour period. It was found that the arterial hydration (fractional mass of water) was 0.740 +/- 0.0043 SEM for control tissue; after 24 hours this rose to 0.745 +/- 0.0038 for 0 mm Hg, 0.752 +/- 0.0046 for 100 mm Hg, and 0.755 +/- 0.0065 for 200 mm Hg. In the transport studies, the following effects were found. The reagent radioactivity concentration and composition did not change with pressure or stirring over the 24-hour period. For unpressurized tissue, the 24-hour normalized uptake [uptake (M mg cm-2) divided by reagent concentration (co mg cm-3)] of albumin was (4.86 +/- 0.43 cm) X 10(-3) from stirred and (5.46 +/- 0.36 cm) X 10(-3) from nonstirred reagent; that of LDL was (0.31 +/- 0.02 cm) X 10(-3) from stirred and (0.37 +/- 0.02 cm) X 10(-3) from nonstirred reagent. Pressurization (100 mm Hg) of the tissue increased albumin uptake by 52% from stirred and by 125% from nonstirred reagent and the LDL uptake by 52% from stirred and 241% from nonstirred reagent. Pressure increased the intimal surface concentration of albumin and LDL at the nonstirred, but not at stirred, interfaces. The electrophoretic properties of the intimal surface fluid showed only minor differences from those of the bulk reagent. These data demonstrate that pressure causes a slight, but significant, increase in arterial hydration and that radiolabeled albumin and LDL appear to be sieved by the superficial intimal layers of the deendothelialized porcine aorta under the in vitro conditions of this study.

Arterial intimal-medial permeability and coevolving structural responses to defined shear-stress exposures

“…Among other things, this normal interstitial state is maintained by the structure-dependent diffusive and convective paths of mass transport across the pressurized endothelial cell layer and its subjacent, gelled matrix system. The normal unpressurized endothelial cell surface and basement membrane act as a diffusive barrier that, when pressurized, also acts as a macromolecular sieving barrier (28,29). In this case, the macromolecular flux becomes "sieved" or retarded with respect to the transmural water flux at the plasma-endothelial interface (27,29).…”

“…In this case, the macromolecular flux becomes "sieved" or retarded with respect to the transmural water flux at the plasma-endothelial interface (27,29). Accordingly, the chemically active concentration of plasma macromolecules at the normal endothelial (or at the basement membrane) interface would become progressively higher than that in the plasma were it not continuously diffused or swept away by the adjacent blood flow (27)(28)(29). Moreover, the associated transendothelial pressure drop related to this sieving is essential for maintenance of an optimal hydration of the compact (gelled) state of the subjacent endothelial-intimal matrix.…”

“…9), a new sieving site will be created. Because this site is sequestered from the blood flow, the resulting accumulation of rejected solutes can rise to abnormally high (chemically active) interstitial concentrations (27)(28)(29). These regions finally reach new but abnormally high steadystate transmural concentration distributions.…”

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.

“…Such disruption would allow a further increase in the intimal diffusive influx and perhaps more importantly, could also allow transendothelial convection of various plasma substances such as LDL, chemotactic agents, growth factors, etc, into the intimal space. 720 ' 39 If there are macromolecular sieving structures in the subjacent intimal layer 28 at such sites, the associated convective tides can result in very high intimal atherogenic chemical activities and activity gradients, 7 -39 particularly in areas of intimal thickening. 7 ' 3234 This scenario suggests only one of several plausible ensembles of events that could relate the observed phenotypically determined normocholesterolemic pattern of endothelial diffusive permeability [F t (z) contour] to the development of intimal sudanophilic lesions, fibrocellular intimal thickening, and the transition of these benign intimal changes into raised atheromatous lesions.…”

Accumulation of 125I-tyramine cellobiose-labeled low density lipoprotein is greater in the atherosclerosis-susceptible region of White Carneau pigeon aorta and further enhanced once atherosclerotic lesions develop.

“…Because albumin (an example of a small protein) equilibrates more rapidly with the artery than do lipoproteins 43 and the concentration of albumin in the artery of normal animals has been estimated to be two to 10 times that of LDL, 44 - 45 it seems likely that the presence of a significant portion of the protein-bound I radioactivity in the HDL-plasma protein fraction would result in significant overestimation of the arterial I-TC content would have entered the artery early after injection when the specific activity of LDL in plasma was high and relatively more of the ^I-TC label was present in the LDL fraction. Third, most of the 125 I-TC label lost from LDL was transferred to VLDL, which at least in humans 47 and rabbits, 48 " 49 enters the artery less rapidly than LDL.…”