The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans.
Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL). The role of the LDL receptor in the catabolism of Lp(a) has been controversial. We therefore investigated the in vivo catabolism of Lp(a) and LDL in five unrelated patients with homozygous familial hypercholesterolemia (FH) who have little or no LDL receptor activity. Purified 125I-Lp(a) and 131I-LDL were simultaneously injected into the homozygous FH patients, their heterozygous FH parents when available, and control subjects. The disappearance of plasma radioactivity was followed over time. As expected, the fractional catabolic rates (FCR) of 131I-LDL were markedly decreased in the homozygous FH patients (mean LDL FCR 0.190 d-1) and somewhat decreased in the heterozygous FH parents (mean LDL FCR 0.294 d-1) compared with controls (mean LDL FCR 0.401 d-1). In contrast, the catabolism of 125I-Lp(a) was not significantly different in the homozygous FH patients (mean FCR 0.251 d-1), heterozygous FH parents (mean FCR 0.254 d-1), and control subjects (mean FCR 0.287 d-1). In summary, absence of a functional LDL receptor does not result in delayed catabolism of Lp(a), indicating that the LDL receptor is not a physiologically important route of Lp(a) catabolism in humans.
Rader
D J
DJ
Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
Mann
W A
WA
Cain
W
W
Kraft
H G
HG
Usher
D
D
Zech
L A
LA
Hoeg
J M
JM
Davignon
J
J
Lupien
P
P
Grossman
M
M
D000328:Adult; D002648:Child; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D011973:Receptors, LDL / Q000172:deficiency*
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011973:Receptors, LDL