University of Oulu

Paavola T, Kuusisto S, Jauhiainen M, Kakko S, Kangas-Kontio T, Metso J, et al. (2017) Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level. PLoS ONE 12(2): e0171993. doi:10.1371/journal.pone.0171993

Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level

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Author: Paavola, Timo1,2; Kuusisto, Sanna3,1,2; Jauhiainen, Matti4;
Organizations: 1Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
2Medical Research Center, Oulu University Hospital, Oulu, Finland
3Current address: NMR metabolomics laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
4Genomics and Biomarkers Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland
5Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland
6NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
7Oulu University Hospital, Oulu, Finland
8Computational Medicine, School of Social and Community Medicine & Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
9Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland
10Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201704116050
Language: English
Published: Public Library of Science, 2017
Publish Date: 2017-04-11
Description:

Abstract

Objective: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD.

Methods: HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum.

Results: While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001).

Conclusion: Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 12
Issue: 2
Article number: e0171993
DOI: 10.1371/journal.pone.0171993
OADOI: https://oadoi.org/10.1371/journal.pone.0171993
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 Internal medicine
Subjects:
Funding: This work was funded by Sigrid Jusélius Foundation (MJS; http://www.sigridjuselius.fi/foundation), Academy of Finland (Grant #132629 to MJ; http://www.aka.fi/en), Finnish Cultural Foundation (TP; https://skr.fi/en), Finnish Foundation for Cardiovascular Research (MJS, TP; http://www.sydantutkimussaatio.fi/en/foundation), Paavo Nurmi Foundation (TP; http://www.paavonurmensaatio.fi/index_e.htm), Foundation of Medical Licentiate Paavo Ilmari Ahvenainen (TP) and Academy of Finland (Grant #257545 to MJ; http://www.aka.fi/en).
Academy of Finland Grant Number: 132629
257545
Detailed Information: 132629 (Academy of Finland Funding decision)
257545 (Academy of Finland Funding decision)
Dataset Reference: All relevant data are within the paper and its Supporting Information files.
Copyright information: © 2017 Paavola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  https://creativecommons.org/licenses/by/4.0/