Intimal retention of cholesterol derived from apolipoprotein B100- and apolipoprotein B48-containing lipoproteins in carotid arteries of Watanabe heritable hyperlipidemic rabbits.

OBJECTIVE The arterial retention of apolipoprotein (apo) B100- and apoB48-containing lipoproteins was simultaneously determined in a rabbit model of human hypercholesterolemia using 3D confocal microscopy. METHODS AND RESULTS Lipoproteins containing apoB100 (LDL) and apoB48 (chylomicron remnants) were differentially conjugated with fluorophores and simultaneously perfused at equivalent concentrations under physiological conditions in situ through carotid vessels of Watanabe heritable hyperlipidemic rabbits and compared with controls. Retention of lipoproteins was defined as the amount remaining after an extensive washout phase. LDL and chylomicron remnants were both retained, primarily within the subendothelial space. Without a concomitant increase in exposure to lipoproteins, we found a marked increase in the retention of cholesterol within the intima of Watanabe heritable hyperlipidemic rabbits compared with controls, specifically because of increased entrapment of apoB48-containing lipoproteins. CONCLUSIONS Collectively, our data suggest that hypercholesterolemia induced as a consequence of LDL receptor deficiency differentially influences retention of LDL and of chylomicron remnants.