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  • Ljunggren, Stefan ALinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten (author)

Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • Elsevier,2015
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-122723
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122723URI
  • https://doi.org/10.1016/j.bbalip.2015.09.006DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agencies: EUs Sixth Framework Program [037631]; European Union [FP7-603091-2]; CardioVascular Research Initiative [CVON2011-16]; Research Council of South East Sweden [FORSS-3755]; County Council of Ostergotland (C-ALF); Faculty of Health Sciences in Linkoping; Ven
  • The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1P297S heterozygotes.Lipoproteins from six SR-B1P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed.Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I.The SR-B1P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Levels, Johannes H MAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Hovingh, KeesAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Holleboom, Adriaan GAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Vergeer, MennoAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Argyri, LettaNational Center for Scientific Research "Demokritos", Athens, Greece (author)
  • Gkolfinopoulou, ChristinaNational Center for Scientific Research "Demokritos", Athens, Greece (author)
  • Chroni, AngelikiNational Center for Scientific Research "Demokritos", Athens, Greece (author)
  • Sierts, Jeroen AAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Kastelein, John JAcademic Medical Centre, Amsterdam, the Netherlands (author)
  • Kuivenhoven, Jan AlbertUniversity of Groningen, University Medical Center Groningen, Groningen, the Netherlands (author)
  • Lindahl, MatsLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten(Swepub:liu)matli17 (author)
  • Karlsson, HelenLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Arbets- och miljömedicin(Swepub:liu)helka90 (author)
  • Linköpings universitetAvdelningen för neuro- och inflammationsvetenskap (creator_code:org_t)

Related titles

  • In:Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids: Elsevier1851:12, s. 1587-15951388-19811879-2618

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