Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]

• Main Authors: William J. Cain, John S. Millar, Adam S. Himebauch, Uwe J.F. Tietge, Cyrille Maugeais, David Usher, Daniel J. Rader
• Format: Article
• Language: English
• Published: Elsevier 2005-12-01
• Series: Journal of Lipid Research
• Subjects: kidney; tissue distribution; kinetics; LDL receptor; apolipoprotein E; asialoglycoprotein receptor
• Online Access: http://www.sciencedirect.com/science/article/pii/S002222752032856X

The cellular and molecular mechanisms responsible for lipoprotein [a] (Lp[a]) catabolism are unknown. We examined the plasma clearance of Lp[a] and LDL in mice using lipoproteins isolated from human plasma coupled to radiolabeled tyramine cellobiose. Lipoproteins were injected into wild-type, LDL receptor-deficient (Ldlr−/−), and apolipoprotein E-deficient (Apoe−/−) mice. The fractional catabolic rate of LDL was greatly slowed in Ldlr−/− mice and greatly accelerated in Apoe−/− mice compared with wild-type mice. In contrast, the plasma clearance of Lp[a] in Ldlr−/− mice was similar to that in wild-type mice and was only slightly accelerated in Apoe−/− mice. Hepatic uptake of Lp[a] in wild-type mice was 34.6% of the injected dose over a 24 h period. The kidney accounted for only a small fraction of tissue uptake (1.3%). To test whether apolipoprotein [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, did not inhibit Lp[a] clearance.In summary, the liver is the major organ accounting for the clearance of Lp[a] in mice, with the LDL receptor and apolipoprotein E having no major roles. Our studies indicate that apo[a] is the primary ligand that mediates Lp[a] uptake and plasma clearance.