Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

Sara Elsøe; Christina Christoffersen; Jayraz Luchoomun; Scott Turner; Lars Bo Nielsen

doi:10.1016/j.bbalip.2013.04.009

Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

Sara Elsøe, Christina Christoffersen, Jayraz Luchoomun, Scott Turner, Lars Bo Nielsen

Physiology of circulation, kidney and lung

25 Citations (Scopus)

Abstract

Objective The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases preβ-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice. Methods and results ApoM-enriched HDL from apoM-transgenic mice increased the in vitro efflux of ³H-cholesterol from macrophages by 24 ± 3% (p < 0.05) as compared with HDL from wild type (WT) mice, thus confirming previous findings. However, apoM-free HDL was not poorer than that of WT HDL to mobilize ³H-cholesterol. ³H-cholesterol-labeled foam cells were implanted in the peritoneal cavity of apoM^-/-, WT and apoM-transgenic mice to assess the mobilization of cholesterol from foam cells in vivo and subsequent excretion into feces. The results showed a statistically non-significant trend towards increased mobilization of cellular cholesterol to plasma with increasing plasma apoM. However, the apoM-genotype did not affect the excretion of ³H-cholesterol in feces. Nevertheless, when apoM^-/-, apoM-transgenic and WT mice received a constant intravenous infusion of ¹³C₂-cholesterol/intralipid for 5 h, the rate of enrichment of blood free cholesterol with free ¹³C ₂-cholesterol was significantly lower (consistent with an increase in flux of unlabeled free cholesterol into the plasma) in the apoM-transgenic (3.0 ± 0.9‰/h) as compared to WT (5.7 ± 0.9‰/h, p < 0.05) and apoM^-/- (6.5 ± 0.6‰/h, p < 0.01) mice. Conclusion The present data indicate that the plasma apoM levels modulate the ability of plasma to mobilize cellular cholesterol, whereas apoM has no major effect on the excretion of cholesterol into feces.

Original language	English
Journal	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume	1831
Issue number	7
Pages (from-to)	1287-92
Number of pages	6
ISSN	1388-1981
DOIs	https://doi.org/10.1016/j.bbalip.2013.04.009
Publication status	Published - Jul 2013

Keywords

Animals
Apolipoproteins
Atherosclerosis
Bile
Cell Line
Cholesterol
Feces
Foam Cells
Gene Deletion
Humans
Lipid Metabolism
Lipoproteins, HDL
Macrophages
Mice
Mice, Inbred C57BL
Mice, Transgenic

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10.1016/j.bbalip.2013.04.009

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@article{7303eb6e0b4a4c68b36d9e6ee915d556,

title = "Apolipoprotein M promotes mobilization of cellular cholesterol in vivo",

abstract = "Objective The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases preβ-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice. Methods and results ApoM-enriched HDL from apoM-transgenic mice increased the in vitro efflux of 3H-cholesterol from macrophages by 24 ± 3% (p < 0.05) as compared with HDL from wild type (WT) mice, thus confirming previous findings. However, apoM-free HDL was not poorer than that of WT HDL to mobilize 3H-cholesterol. 3H-cholesterol-labeled foam cells were implanted in the peritoneal cavity of apoM-/-, WT and apoM-transgenic mice to assess the mobilization of cholesterol from foam cells in vivo and subsequent excretion into feces. The results showed a statistically non-significant trend towards increased mobilization of cellular cholesterol to plasma with increasing plasma apoM. However, the apoM-genotype did not affect the excretion of 3H-cholesterol in feces. Nevertheless, when apoM-/-, apoM-transgenic and WT mice received a constant intravenous infusion of 13C2-cholesterol/intralipid for 5 h, the rate of enrichment of blood free cholesterol with free 13C 2-cholesterol was significantly lower (consistent with an increase in flux of unlabeled free cholesterol into the plasma) in the apoM-transgenic (3.0 ± 0.9‰/h) as compared to WT (5.7 ± 0.9‰/h, p < 0.05) and apoM-/- (6.5 ± 0.6‰/h, p < 0.01) mice. Conclusion The present data indicate that the plasma apoM levels modulate the ability of plasma to mobilize cellular cholesterol, whereas apoM has no major effect on the excretion of cholesterol into feces.",

keywords = "Animals, Apolipoproteins, Atherosclerosis, Bile, Cell Line, Cholesterol, Feces, Foam Cells, Gene Deletion, Humans, Lipid Metabolism, Lipoproteins, HDL, Macrophages, Mice, Mice, Inbred C57BL, Mice, Transgenic",

author = "Sara Els{\o}e and Christina Christoffersen and Jayraz Luchoomun and Scott Turner and Nielsen, {Lars Bo}",

year = "2013",

month = jul,

doi = "10.1016/j.bbalip.2013.04.009",

language = "English",

volume = "1831",

pages = "1287--92",

journal = "Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids",

issn = "1388-1981",

publisher = "Elsevier",

number = "7",

}

TY - JOUR

T1 - Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

AU - Elsøe, Sara

AU - Christoffersen, Christina

AU - Luchoomun, Jayraz

AU - Turner, Scott

AU - Nielsen, Lars Bo

PY - 2013/7

Y1 - 2013/7

N2 - Objective The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases preβ-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice. Methods and results ApoM-enriched HDL from apoM-transgenic mice increased the in vitro efflux of 3H-cholesterol from macrophages by 24 ± 3% (p < 0.05) as compared with HDL from wild type (WT) mice, thus confirming previous findings. However, apoM-free HDL was not poorer than that of WT HDL to mobilize 3H-cholesterol. 3H-cholesterol-labeled foam cells were implanted in the peritoneal cavity of apoM-/-, WT and apoM-transgenic mice to assess the mobilization of cholesterol from foam cells in vivo and subsequent excretion into feces. The results showed a statistically non-significant trend towards increased mobilization of cellular cholesterol to plasma with increasing plasma apoM. However, the apoM-genotype did not affect the excretion of 3H-cholesterol in feces. Nevertheless, when apoM-/-, apoM-transgenic and WT mice received a constant intravenous infusion of 13C2-cholesterol/intralipid for 5 h, the rate of enrichment of blood free cholesterol with free 13C 2-cholesterol was significantly lower (consistent with an increase in flux of unlabeled free cholesterol into the plasma) in the apoM-transgenic (3.0 ± 0.9‰/h) as compared to WT (5.7 ± 0.9‰/h, p < 0.05) and apoM-/- (6.5 ± 0.6‰/h, p < 0.01) mice. Conclusion The present data indicate that the plasma apoM levels modulate the ability of plasma to mobilize cellular cholesterol, whereas apoM has no major effect on the excretion of cholesterol into feces.

AB - Objective The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases preβ-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice. Methods and results ApoM-enriched HDL from apoM-transgenic mice increased the in vitro efflux of 3H-cholesterol from macrophages by 24 ± 3% (p < 0.05) as compared with HDL from wild type (WT) mice, thus confirming previous findings. However, apoM-free HDL was not poorer than that of WT HDL to mobilize 3H-cholesterol. 3H-cholesterol-labeled foam cells were implanted in the peritoneal cavity of apoM-/-, WT and apoM-transgenic mice to assess the mobilization of cholesterol from foam cells in vivo and subsequent excretion into feces. The results showed a statistically non-significant trend towards increased mobilization of cellular cholesterol to plasma with increasing plasma apoM. However, the apoM-genotype did not affect the excretion of 3H-cholesterol in feces. Nevertheless, when apoM-/-, apoM-transgenic and WT mice received a constant intravenous infusion of 13C2-cholesterol/intralipid for 5 h, the rate of enrichment of blood free cholesterol with free 13C 2-cholesterol was significantly lower (consistent with an increase in flux of unlabeled free cholesterol into the plasma) in the apoM-transgenic (3.0 ± 0.9‰/h) as compared to WT (5.7 ± 0.9‰/h, p < 0.05) and apoM-/- (6.5 ± 0.6‰/h, p < 0.01) mice. Conclusion The present data indicate that the plasma apoM levels modulate the ability of plasma to mobilize cellular cholesterol, whereas apoM has no major effect on the excretion of cholesterol into feces.

KW - Animals

KW - Apolipoproteins

KW - Atherosclerosis

KW - Bile

KW - Cell Line

KW - Cholesterol

KW - Feces

KW - Foam Cells

KW - Gene Deletion

KW - Humans

KW - Lipid Metabolism

KW - Lipoproteins, HDL

KW - Macrophages

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

U2 - 10.1016/j.bbalip.2013.04.009

DO - 10.1016/j.bbalip.2013.04.009

M3 - Journal article

C2 - 24046869

SN - 1388-1981

VL - 1831

SP - 1287

EP - 1292

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

IS - 7

ER -

Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

Abstract

Keywords

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