Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta.

Abstract

Normal rabbits were injected Intravenously with horseradish peroxldase (HRP) and 125 l-labeled human low density lipoprotein (LDL), and the aortas were pertuslon-flxed. Subsequent visualization of HRP In the aortas was produced by reaction of the tissue with diaminobenzldine and hydrogen peroxide. The lumlnal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall. The foci were scattered over the luminal surface, and most of the focal areas were less than 1 mm In diameter. The concentration of LDL was up to 47 times greater in these focal areas than in surrounding noncolored regions not showing Increased permeability to HRP. Small circumscribed foci of heightened permeability to LDL may predispose to the local accumulation of llpld and ultimately to the formation of atherosclerotic plaques. (Arteriosclerosis 6:64-69, January/February 1986) T wo salient features of atherosclerotic lesions are the focal nature of plaque formation and the accumulation of cholesterol, cholesterol esters, triglycerides, and other lipids. The process by which atherosclerotic lesions originate is poorly understood. It is possible, however, that endothelial injury leading to increased arterial wall permeability could be a first stage in atherogenesis. In vivo studies with the protein-binding dye Evans blue 1 " 3 have shown that the dye is taken up preferentially by certain regions of the aortas of rabbits, dogs, and pigs. In pigs these relatively broad regions of enhanced permeability have also been shown to incorporate

Inhibition of atherosclerosis associated with reduction of arterial intramural stress in rabbits.

“…Ross mentioned that endothelial injury could result in release of growth factors, which could provide a mitogenic stimulus to smooth muscle cells. Stemerman et al 41 pointed out that gross endothelial damage is not necessary to mediate a large local increase in the uptake of low density lipoprotein (LDL). The term, endothelial injury, has also been used to indicate endothelial cell dysfunction.…”

Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia

“…One of the first issues that one must address to develop an understanding of the mass transport in these vessels is whether such transport is driven by diffusion and/or convection. In previous mass transport studies of the aorta, rats were injected with a macromolecular tracer, such as horseradish peroxidase (HRP), and were killed after different circulation times (11,35). In an examination of the animals' aortas en face, HRP was found to traverse the endothelium in rare localized spots, rather than uniformly.…”

Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase.

“…Previous investigation with horseradish peroxidase (HRP) has revealed brown spots with an LDL concentration 47 times greater than the noncolored regions after a short circulation time, but the nature of those leaky spots has not been elucidated. 5 More recently, it has been shown that almost all mitotic cells in aortic endothelium are leaky to EBA, 6 but the data were not analyzed in terms of their regional distribution, the process of lateral diffusion, or hemodynamic influences. To address the questions of: 1) the initial sites of macromolecular entry, 2) the process of lateral diffusion in the media of vessel wall, and 3) the hemodynamic influences on atherogenesis, we used EBA and HRP as tracers to study the macromolecular transport across arterial and venous endothelia in normal rats.…”