title: The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles.
abstract: ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P = 0.02, respectively) as compared with noncarriers (0.93 ± 0.04 µM). When we injected human apoM-containing HDL into Wt (n = 6) or LDL receptor-deficient mice (n = 6), the removal of HDL-associated human apoM was delayed in the LDL receptor-deficient mice. After 2 h, 54 ± 5% versus 90 ± 8% (P < 0.005) of the initial amounts of human apoM remained in the plasma of Wt and LDL receptor-deficient mice, respectively. Finally, we compared the turnover of radio-iodinated LDL and plasma apoM concentrations in 45 normocholesterolemic humans. There was a negative correlation between plasma apoM and the fractional catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles.
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors: Christina
authors: C
authors: Christoffersen
authors: Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
authors: Marianne
authors: M
authors: Benn
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors: Pernille M
authors: PM
authors: Christensen
authors: Center of Human Genetics, Experimental Mouse Genetics, Katholieke Universiteit, Leuven, Belgium.
authors: Philip L S M
authors: PLSM
authors: Gordts
authors: Center of Human Genetics, Experimental Mouse Genetics, Katholieke Universiteit, Leuven, Belgium.
authors: Anton J M
authors: AJM
authors: Roebroek
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors: Ruth
authors: R
authors: Frikke-Schmidt
authors: Department of Laboratory Medicine, Wallenberg Laboratory, Skåne University Hospital, Lund University, Malmö, Sweden; and.
authors: Anne
authors: A
authors: Tybjaerg-Hansen
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. Electronic address: bjorn.dahlback@med.lu.se.
authors: Björn
authors: B
authors: Dahlbäck
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: larsbo@rh.dk.
authors: Lars B
authors: LB
authors: Nielsen
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D000075243:Apolipoproteins M; D005260:Female; D006801:Humans; D054834:Lipocalins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011446:Prospective Studies; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D001055:Apolipoproteins B; D000075243:Apolipoproteins M; D054834:Lipocalins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL