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The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles

På svenska

Author

  • Christina Christoffersen
  • Marianne Benn
  • Pernille M. Christensen
  • Philip L. S. M. Gordts
  • Anton J. M. Roebroek
  • Ruth Frikke-Schmidt
  • Anne Tybjaerg-Hansen
  • Björn Dahlbäck
  • Lars B. Nielsen

Summary, in English

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 mu M, P = 0.003, and 1.23 +/- 0.10 mu M, P = 0.02, respectively) as compared with noncarriers (0.93 +/- 0.04 mu M). 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.-Christoffersen, C., M. Benn, P. M. Christensen, P. L. S. M. Gordts, A. J. M. Roebroek, R. Frikke-Schmidt, A. Tybjaerg-Hansen, B. Dahlback, and L. B. Nielsen. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles. J. Lipid Res. 2012. 53: 2198-2204.

Publishing year

2012

Language

English

Pages

2198-2204

Publication/Series

Journal of Lipid Research

Volume

53

Issue

10

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Medicinal Chemistry

Keywords

  • lipoprotein
  • low-density lipoprotein metabolism
  • apolipoprotein
  • familial hypercholesterolemia

Status

Published

Research group

  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1539-7262