Functional alteration of endothelium by short-term cholesterol feeding

The influence of varying periods of cholesterol feeding and of superimposed endothelial denudation on the transmural transport of albumin has been studied in rabbit carotid artery perfused in vivo with Dulbecco's modified Eagle's medium. The concentration of labeled albumin in jugular venous blood was measured serially over 4 hr and was used as the index of arterial transport. Three groups of rabbits were fed a diet containing 1.5% cholesterol for either 1, 3-7, or 12-28 weeks. A significant increase in albumin transport across the carotid artery was noted in all groups when compared to control animals who were fed a standard rabbit chow. The transport abnormalities observed after 1 week occurred in the absence of any grossly visible atherosclerotic lesions or of any evidence of endothelial cell loss by scanning electron microscopy. In an additional group of rabbits who were fed the cholesterol diet for 16-28 weeks and in which endothelial denudation was performed just prior to carotid perfusion, removal of carotid artery endothelium did not cause a further enhancement of albumin transport above that observed by cholesterol feeding alone. The findings suggest that cholesterol feeding of even very brief duration can alter endothelial function and enhance arterial permeability to albumin.