An ultrastructural study of beta-very low density lipoprotein uptake and transport by valvular endothelium of hyperlipidemic rabbits.

The uptake and transport of beta-VLDL by the aortic valvular endothelium of normal and hypercholesterolemic rabbits were studied in situ. The rabbits were fed either standard diet or standard diet supplemented with 0.5% cholesterol and 10% butter, for 1-20 weeks. Rabbit beta-VLDL was either radiolabeled with 125I or conjugated with colloidal gold (Au) (5 nm-diameter size). beta-VLDL-Au or [125I]-beta-VLDL was perfused in situ via left ventricle and maintained within heart and thoracic aorta for 15 to 60 min at 37 degrees C. Small pieces of aortic valve tissue were processed for electron microscopy or for electron microscopic autoradiography according to the lipoprotein probe used. beta-VLDL was taken and transported by the valvular endothelium of normal or hypercholesterolemic animals by endocytosis and transcytosis. As compared to normal animals, the endocytosis of beta-VLDL by the aortic valvular endothelium of hypercholesterolemic animals started to increase after 2-3 weeks of diet, being almost double in the 12th week of diet. Quantification of autoradiographic grains indicated a marked augmentation of beta-VLDL particles transcytosed by plasmalemmal vesicles of hypercholesterolemic animals as compared to normal. In the aortic valves of hyperlipidemic animals, the amount of beta-VLDL transported through the endothelium of fibrosa region was 3 times higher than that of spongiosa region of the same valve. The results showed that in hyperlipidemia, beta-VLDL transcytosis is generally markedly enhanced, in particular in lesion prone area.