Hepatic Lipase Deficiency Increases Plasma Cholesterol but Reduces Susceptibility to Atherosclerosis in Apolipoprotein E-deficient Mice

Mezdour, Hafid; Jones, Robert; Dengremont, Catherine; Castro, Graciela; Maeda, Nobuyo

doi:10.1074/jbc.272.21.13570

Cited by 113Lipid metabolism and disordersCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Hepatic Lipase Deficiency Increases Plasma Cholesterol but Reduces Susceptibility to Atherosclerosis in Apolipoprotein E-deficient Mice

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Mezdour, Hafid, Jones, Robert, Dengremont, Catherine, Castro, Graciela, Maeda, Nobuyo·1997·Journal of Biological Chemistry

DOI 10.1074/jbc.272.21.13570

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Abstract

The effect of hepatic lipase (HL) deficiency on the susceptibility to atherosclerosis was tested using mice with combined deficiencies in HL and apoE. Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/- 252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/- 161 mg/dl, n = 20, p < 0. 001). The increase in cholesterol was mainly in beta-migrating very low density lipoproteins, although high density lipoprotein cholesterol (HDLc) was also increased (53 +/- 37 versus 20 +/- 13 mg/dl, p < 0.01). Despite the increase in plasma cholesterol, we found that HL deficiency significantly decreased aortic plaque sizes in female mice fed normal chow (31 x 10(3) +/- 22 x 10(3) microm2 in hhee versus 115 x 10(3) +/- 69 x 10(3) microm2 in HHee, p < 0.001). Reduction of plaque sizes was also observed in female heterozygous apoE-deficient mice fed an atherogenic diet (2 x 10(3) +/- 2.5 x 10(3) microm2 in hhEe versus 56 x 10(3) +/- 49 x 10(3) microm2 in HHEe, p < 0.01). Changes in aortic lesion size were not apparent in the small number of male mice studied. In HHee females, both HDLc and the capacity of high density lipoprotein (HDL) particles to promote cholesterol efflux from cultured cells were 26% of the wild type. The absence of HL in hhee females partially restored HDLc levels to 57% and cholesterol efflux to 55% of the wild type. Circulating pre-beta1-migrating HDL were present in all mutants, suggesting that there are alternative pathways in the formation of these pre-beta-HDL not involving apoE, HL, or cholesteryl ester transfer protein. The improved capacity to promote cholesterol efflux, together with increased HDL, may explain why these animals can overcome the increase in atherogenic lipoproteins.

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The patient had a large increase in small HDL species, particularly prebeta-1 HDL, analogous to observations with ApoE knockout mice.
“We observed a large increase in small HDL species in our patient’s plasma, particularly prebeta-1 HDL, analogous to observations with ApoE knockout mice.33”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [33]

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Authors: Mezdour, H., Jones, R., Dengremont, C., Castro, G., & Maeda, N.
Affiliations: University of North Carolina at Chapel Hill (US)
Institut Pasteur (FR)
Corresponding author: Maeda, Nobuyo
ORCID: Maeda, Nobuyo
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1997-05
Volume: 272
Issue: 21
Pages: 13570-13575
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.272.21.13570
OpenAlex: W2071388690
Cited by: 113
References: 34
Citations by year: 2026: 1 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 3
FWCI: 6.00
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 8566 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL 42630)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords: apolipoprotein E deficiency, atherosclerosis susceptibility, serum cholesterol, HDL cholesterol, cholesterol efflux, aortic plaque, VLDL, prebeta-HDL, atherogenic diet, sex differences, cholesteryl ester transfer protein, lipoprotein metabolism, atheroprotection
MeSH terms: Animals, Apolipoproteins E, Arteries, Arteriosclerosis, Cholesterol, Electrophoresis, Agar Gel, Female, Lipase, Lipids, Lipoproteins, Lipoproteins, HDL, Liver, Male, Mice, Mutant Strains, Mice

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Hepatic Lipase Deficiency Increases Plasma Cholesterol but Reduces Susceptibility to Atherosclerosis in Apolipoprotein E-deficient Mice

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