出版社：American Society for Biochemistry and Molecular Biology
摘要：The cellular and molecular mechanisms responsible for lipoprotein[a] (Lp[a]) catabolism are unknown. We examined the plasma clearanceof Lp[a] and LDL in mice using lipoproteins isolated from humanplasma coupled to radiolabeled tyramine cellobiose. Lipoproteinswere injected into wild-type, LDL receptor-deficient (Ldlr–/–),and apolipoprotein E-deficient (Apoe–/–) mice. Thefractional catabolic rate of LDL was greatly slowed in Ldlr–/–mice and greatly accelerated in Apoe–/– mice comparedwith wild-type mice. In contrast, the plasma clearance of Lp[a]in Ldlr–/– mice was similar to that in wild-typemice and was only slightly accelerated in Apoe–/–mice. Hepatic uptake of Lp[a] in wild-type mice was 34.6% ofthe injected dose over a 24 h period. The kidney accounted foronly a small fraction of tissue uptake (1.3%). To test whetherapolipoprotein [a] (apo[a]) mediates the clearance of Lp[a]from plasma, we coinjected excess apo[a] with labeled Lp[a].Apo[a] acted as a potent inhibitor of Lp[a] plasma clearance.Asialofetuin, a ligand of the asialoglycoprotein receptor, didnot inhibit Lp[a] clearance.
In summary, the liver is the major organ accounting for theclearance of Lp[a] in mice, with the LDL receptor and apolipoproteinE having no major roles. Our studies indicate that apo[a] isthe primary ligand that mediates Lp[a] uptake and plasma clearance.Supplementary key words kidney • tissue distribution • kinetics • LDL receptor • apolipoprotein E • asialoglycoprotein receptor
