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

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

doi:10.1194/jlr.P023697

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

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

26 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Lipid Research
Vol/bind	53
Udgave nummer	10
Sider (fra-til)	2198-204
Antal sider	7
ISSN	0022-2275
DOI	https://doi.org/10.1194/jlr.P023697
Status	Udgivet - okt. 2012

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10.1194/jlr.P023697

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Christoffersen, C., Benn, M., Christensen, P. M., Gordts, P. L. S. M., Roebroek, A. J. M., Frikke-Schmidt, R., Tybjaerg-Hansen, A., Dahlbäck, B., & Nielsen, L. B. (2012). The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles. Journal of Lipid Research, 53(10), 2198-204. https://doi.org/10.1194/jlr.P023697

@article{c674e3fecaed4be99d52fa8a0b7ca460,

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.",

author = "Christina Christoffersen and Marianne Benn and Christensen, {Pernille M{\o}ller} and Gordts, {Philip L S M} and Roebroek, {Anton J M} and Ruth Frikke-Schmidt and Anne Tybjaerg-Hansen and Bj{\"o}rn Dahlb{\"a}ck and Nielsen, {Lars B}",

year = "2012",

month = oct,

doi = "10.1194/jlr.P023697",

language = "English",

volume = "53",

pages = "2198--204",

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TY - JOUR

T1 - The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles

AU - Christoffersen, Christina

AU - Benn, Marianne

AU - Christensen, Pernille Møller

AU - Gordts, Philip L S M

AU - Roebroek, Anton J M

AU - Frikke-Schmidt, Ruth

AU - Tybjaerg-Hansen, Anne

AU - Dahlbäck, Björn

AU - Nielsen, Lars B

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

U2 - 10.1194/jlr.P023697

DO - 10.1194/jlr.P023697

M3 - Journal article

SN - 0022-2275

VL - 53

SP - 2198

EP - 2204

JO - Journal of Lipid Research

JF - Journal of Lipid Research

IS - 10

ER -

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

Abstract

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