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

Christoffersen, Christina; Benn, Marianne; Christensen, Pernille M.; Gordts, Philip L. S. M.; Roebroek, Anton J. M.; Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Dahlbäck, Björn LU and Nielsen, Lars B. (2012) In Journal of Lipid Research 53(10). p.2198-2204
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 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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lipoprotein, low-density lipoprotein metabolism, apolipoprotein, familial hypercholesterolemia
in
Journal of Lipid Research
volume
53
issue
10
pages
2198 - 2204
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • wos:000308696600019
  • scopus:84866178749
ISSN
1539-7262
DOI
10.1194/jlr.P023697
language
English
LU publication?
yes
id
dd36f218-6658-46a5-a349-332cf085954d (old id 3135932)
date added to LUP
2012-11-01 16:55:25
date last changed
2017-09-24 03:19:00
@article{dd36f218-6658-46a5-a349-332cf085954d,
  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 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 &lt; 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.},
  author       = {Christoffersen, Christina and Benn, Marianne and Christensen, Pernille M. and Gordts, Philip L. S. M. and Roebroek, Anton J. M. and Frikke-Schmidt, Ruth and Tybjaerg-Hansen, Anne and Dahlbäck, Björn and Nielsen, Lars B.},
  issn         = {1539-7262},
  keyword      = {lipoprotein,low-density lipoprotein metabolism,apolipoprotein,familial hypercholesterolemia},
  language     = {eng},
  number       = {10},
  pages        = {2198--2204},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Journal of Lipid Research},
  title        = {The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles},
  url          = {http://dx.doi.org/10.1194/jlr.P023697},
  volume       = {53},
  year         = {2012},
}