Summary
The objective of this study was to compare for the first time, by means of electron microscopic autoradiography, the movements of orally administered labelled cholesterol across (a) normal arterial and capillary endothelium, and (b) normal and pathological arterial endothelium.
For this purpose, 15 mCi/kg 3H-Cholesterol, spread in 5 daily doses, was given by stomach tube to (a) normal, (b) chronically hyperlipemic-atherosclerotic, (c) serum sick, and (d) desoxycorticosterone (DOCA) treated rabbits. The animals were killed 6 hours after the last 3H-Cholesterol feeding and thick unstained sections from their glutaraldehyde-digitonin fixed aortae, coronaries, myocardium and liver were then coated with a photographic emulsion, exposed for 2 or 6 months and examined electron-microscopically.
It was found that in normal animals only very few labelled cholesterol molecules crossed the arterial endothelium, whereas large numbers of them crossed the capillary endothelium to enter the muscle cells of the heart and the hepatocytes of the liver. In contrast to the normal arterial endothelium, however, the arterial endothelium of hyperlipemic-atherosclerotic, serum sick and DOCA treated rabbits proved highly permeable to the labelled cholesterol molecules, allowing them to pour in great numbers into the arterial wall. The labelled lipid crossed the endothelium mainly trans-cytoplasmically, but in animals exposed to protracted hyperlipemia it also entered the arterial wall through opened interendothelial junctions that were occasionally observed in this condition.
These results show that the normal arterial endothelium, unlike that of normal capillaries, has a very low permeability for physiologically presented cholesterol (or lipoprotein) molecules, but that certain pathological conditions such as protracted hyperlipemia, hypertension and immune insults change it and make it highly permeable to these molecules.
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This study was supported by grants of the Medical Research Council of Canada and the British Columbia Heart Foundation. Miss Rosalee Watson provided able technical assistance.
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Constantinides, P., Wiggers, K.D. Electron microscopic autoradiographic study of cholesterol passage across arterial and capillary endothelium. Virchows Arch. A Path. Anat. and Histol. 362, 291–310 (1974). https://doi.org/10.1007/BF00427078
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DOI: https://doi.org/10.1007/BF00427078