Enhanced accumulation and turnover of esterified cholesterol in injured rabbit aorta.

Abstract

Several hypotheses have been advanced as possible explanations for the effects of injury. One of these 8 is that removal of the endothelium eliminates a barrier to influx of macromolecules from plasma. Others 9 argue that the endothelium prevents efflux of macromolecules from the artery. At present, relatively few studies have considered the contribution of plasma cholesteryl ester influx to the observed excess cholesteryl ester accumulating in the artery This work was supported by Research Grant HL10933 from the National Heart, Lung and Blood Institute of the United States Public Health Service. Donald B. Zilversmit is a Career Investigator of the American Heart Association. Dawn C. Schwenke held a National Science Foundation Graduate Fellowship during these studies.Received April 17, 1986; revision accepted March 18, 1987. after injury. Most of the measurements of cholesteryl ester influx 3 or lipoprotein accumulation 1011 into previously injured areas of the arterial wall have been made at relatively long times (months) after injury. At these times, the composition of the arterial wall In both reendothelialized areas and those remaining deendothelialized is considerably altered compared with uninjured areas.2 ' 7 1 2 1 3 Several studies suggest that the atherosclerosis risk factors, hypercholesterolemia 14 ' 15 and hypertension, 16 injure the arterial endothelium.Other studies 10 have measured the ability of acutely deendothelialized arterial tissue to limit the accumulation of low density lipoprotein (LDL) in vivo. Yet others 17 have studied the uptake of LDL by perfused vessels. The present investigation addresses the question of whether removal of aortic endothelium and perhaps underlying elements affect cholesteryl ester accumulation primarily by reducing the barrier to influx or to efflux of cholesteryl ester, or both. Specifically we have asked: 1) Does injury to the luminal surface of the artery result in enhanced cholesteryl ester influx in the injured artery? 2) If cholesteryl ester influx is elevated in injured areas, does the cholesteryl ester content of these areas increase concomitantly with the enhanced influx? 3) Is cholesteryl ester turnover altered in injured areas? Methods ChemicalsAll chemicals were reagent grade. Cholesterol methyl ether, 99% pure, (A 5 -cholesten-3G-ol-36-methyl) was pur-

Accelerated cholesterol accumulation in homologous arterial transplants in cholesterol-fed rabbits. A surgical model to study transplantation atherosclerosis.

“…medial layer of the artery, these investigators observed a 30-60-fold increase in permeability to cholesteryl ester, primarily reflecting p-VLDL permeability immediately after injury. 13 If we assume that the HDL permeability of the artery as measured in the present study also reflects the permeability of the much larger /3-VLDL, then the permeability increase immediately after transplantation as observed in our study suggests that transplantation changes the surface of the artery in a manner similar to a more severe physical injury to the artery. The assumption about the proportionality between aortic permeability to HDL and aortic permeability to VLDL is based on findings in nontransplanted aortas of cholesterol-fed rabbits.…”

“…Such studies may have more general interest, as immune mechanisms may also be of importance for the development of the atherosclerotic plaque in nontransplanted arteries. 13 …”

Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta.

“…Two previous studies have estimated uncertainties in calculated values of intimal clearance and fractional loss that are induced by measurement uncertainties of the order likely in practice (24,26), using experimental conditions quite similar to the present study. Wootton et al (24) appplied random noise with zero mean and 1.5% SD to plasma radioacitvity data and random noise of zero mean and 5% SD to arterial wall radioactivity data, which produced uncertainties of 7% SD in calculated intimal clearance and 16% SD in cal-…”

“…Schwenke and Zilversmit (26) estimated that a 5% error in arterial wall radioactivity would produce an 8.5 to 14.5% error in calculated fractional loss and a 1.5 to 10% error in calculated intimal clearance (data calculated from Table 2 in reference 26).…”

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

“…27 It is possible that complex flow patterns behind the aortic valves in the aortic arch may also help explain the high permeability values in this aortic region. Experimental endothelial injury with a balloon catheter increased the influx of lipoproteins into the arterial wall, 29 and in the rat aorta, 37% of arterial foci with high permeability to Evans blue-labeled albumin were associated with endothelial cell death. 30 In the normal rabbit thoracic aorta, endothelial cell death is predominant in the lesion-prone sites.…”