Aortic permeability to LDL as a predictor of aortic cholesterol accumulation in cholesterol-fed rabbits.

Abstract

The aim of this study was to investigate the possibility that the permeability characteristics of the arterial wall are related to the development of atherosclerosis. The in vivo regional variation of aortic permeability to iodinated human low density lipoprotein (LDL) in normal rabbits was compared with the regional variation in aortic cholesterol accumulation in cholesterol-fed rabbits. Aortas were divided into the aortic arch, thoracic aorta, and abdominal aorta, and each of these three parts was further subdivided into four segments of similar size. The permeability to LDL was 40±7 nl • cm" 2 • hr" 1 (mean±SEM, n=ll) in the most proximal segment of the aortic arch and decreased throughout the length of the aorta to 3±1 nl • cm" 2 • hr" 1 in the most caudal segment of the abdominal aorta. In such normal rabbits the aortic cholesterol content was similar in all 12 arterial segments at 0.08 ±0.005 /unol/cm 1 (mean±SEM, n=3xL2). Aortic cholesterol accumulation was determined in other rabbits with an average plasma cholesterol level of 32±1 mmol/l for 96 days; the cholesterol content in the most proximal segment of the aortic arch was 2.7±0.5 fimo\/cm 2 (mean±SEM, n = ll) and decreased with increasing distance from the heart to 0.17±0.03 fisnol/cm 1 in the most caudal segment of the abdominal aorta. Linear regression analysis showed a close positive association between the permeability to LDL of a given aortic segment and the cholesterol accumulation in that same aortic segment after cholesterol feeding (r 2 =0.96, p<0.001). These results suggest that the aortic permeability to LDL is an important predictor for the development of atherosclerosis in cholesterol-fed rabbits. (Arteriosclerosis and Thrombosis 1992;12:1402-1409 KEY WORDS • aortic permeability • atherosclerosis • cholesterol-fed rabbits • LDLs I t is well established that atherosclerotic lesions are characterized by cholesterol accumulation, an increase in intercellular matrix, and cell proliferation. Several lines of evidence from both rabbit and human studies support the conclusion that the cholesterol in atherosclerotic lesions is derived from plasma hpoproteins.1 " 5 In humans as well as rabbits, there is considerable variation in the extent and severity of atherosclerotic lesions between different arterial sites, even though all arterial surfaces within a given individual or rabbit have been exposed to the same plasma cholesterol level.6 -9 This suggests that regional variation in lipoprotein-arterial wall interactions is important for the development of atherosclerosis. Such differences between lesion-resistant and lesion-prone arterial sites could be caused by differences in arterial lipoprotein influx, retention, degradation, or efflux. Differences in arterial lipoprotein influx between arterial sites would be reflected in differences in aortic permeability between these sites. The present study considers the hypothesis that the aortic permeability to human low density lipoprotein (LDL) is a predictor of aortic cholesterol accumulation in chole...

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17β-Estradiol

“…This approach enabled us to precisely manipulate the compositions of the perfusate and superfusate solutions and carefully control arterial flow and hydrostatic pressure, hemodynamic parameters known to influence LDL flux into the artery wall. 7,8,37 The approach that we have taken enabled us to study the mechanisms of LDL flux into the artery wall and is a bridge between previous in vitro and cell culture experiments and experiments performed on whole-animal preparations. 5,18,38 The literature suggests that LDL is primarily modified in the arterial wall because of the large antioxidant capacity of the blood.…”

“…[1][2][3] Sites of relative increase in LDL permeability have been identified in normal arteries 4 and can be induced by injury to the endothelium. [5][6][7][8][9] Alternatively, others have reported increased binding and decreased efflux of LDL from the vascular wall, even under conditions where LDL influx was not affected. 10,11 Therefore, LDL accumulation in the artery wall potentially occurs by several mechanisms, perhaps depending on the stage of atheroma formation.…”

Direct Assessment of Lipoprotein Outflow From In Vivo–Labeled Arterial Tissue as Determined in an In Vitro Perfusion System

“…However, it is disturbing that an increased accumulation due to lipoprotein binding would lead to a flattening of the uptake-versus-time curve, which would give too low rather than too high an estimate of the fractional loss. One way to reconcile these observations is to introduce a "very fast equilibrating pool" or to adopt the concept of plasma contamination 23 ( Figure 5). This would lead to high uptake at early (3 hours) time points, thus restoring the shape of the curve, whereby the 2 types of errors might actually tend to cancel each other.…”

Glycosaminoglycan fractions from human arteries presenting diverse susceptibilities to atherosclerosis have different binding affinities to plasma LDL.

“…9 Still, arterial geometry and pressure are not sufficient to explain the localization of lesions, since major areas of high risk for atherosclerosis also occur away from the ostia and bifurcations 10 and some arteries subjected to normal arterial blood pressure are little affected by atherosclerosis. 3 -3 In fact, studies with experimental animals have demonstrated that low-density lipoprotein (LDL) metabolism, 11 endothelial permeability to LDL, 12 the glycoprotein coating of endothelial cells, 13 and the activity of acid cholesterol esterase 14 vary among vessels, and this variation could be related to differences in atherosclerosis susceptibility. A further aspect of arterial constitution that has been correlated with regional differences in the incidence of atherosclerosis is the degree of folding of the internal elastic membrane in humans, 15 which somehow reflects the amount of elastin in the vessel wall.…”