CHYLOMICRONS OR THEIR REMNANTS PENETRATE RABBIT THORACIC AORTA AS EFFICIENTLY AS DO SMALLER MACROMOLECULES, INCLUDING LOW-DENSITY-LIPOPROTEIN, HIGH-DENSITY-LIPOPROTEIN, AND ALBUMIN

Background: The aortic accumulation of chylomicrons, low-density lipop rotein (LDL), high-density lipoprotein (HDL) and albumin were compared in normal New Zealand White rabbits. Methods: Lipoproteins and albumi n were labelled with radioiodinated tyramine cellobiose (TC) to avoid potential oxidative modification of lipoproteins and as a marker of in tracellular degradation. In preliminary experiments it was established that TC labelling did not alter the kinetic properties of lipoprotein s in vivo. Importantly, radiolabelled apolipoproteins did not transfer significantly between plasma lipoproteins. Therefore, aortic radioact ivity following infusion of TC-radiolabelled lipoproteins was consider ed to be indicative of lipoprotein accumulation. Results: In conscious rabbits, net aortic accumulation of chylomicrons or their remnants wa s similar to those of LDL, HDL and albumin up to 2h after infusion, de spite rapid clearance from plasma. When accumulation was calculated on the basis of mean arterial exposure to allow for the differences in p lasma clearance, the accumulation of aortic chylomicrons/remnants was substantially greater than that of LDL, HDL or albumin. Qualitatively similar results were obtained in rabbits that were functionally evisce rated to slow clearance of chylomicron remnants. Chylomicrons/remnants did not appear to efflux from aortic tissue as rapidly as did LDL or other plasma lipoproteins. Autoradiographic analysis showed that the p rimary site of lipoprotein accumulation was within medial smooth muscl e cells. Conclusion: Our data demonstrate that chylomicrons/remnants a ccumulate in arterial blood vessels more rapidly than does LDL, sugges ting that dietary lipoproteins may be directly involved in the pathoge nesis of atherosclerosis.