title: Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Paavola
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Kuusisto
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Sakari
authors.initials: S
authors.lastname: Kakko
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Tiia
authors.initials: T
authors.lastname: Kangas-Kontio
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Oulu University Hospital, Oulu, Finland.|Computational Medicine, School of Social and Community Medicine & Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.|Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland.
authors.forename: Minna L
authors.initials: ML
authors.lastname: Hannuksela
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Tuire
authors.identifier: http://orcid.org/0000-0001-5104-5792
authors.initials: T
authors.lastname: Salonurmi
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology*; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL