Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model

Joya E. Nahon*, Menno Hoekstra, Stefan R. Havik, Peter J. Van Santbrink, Geesje M. Dallinga-Thie, Jan-Albert Kuivenhoven, Janine J. Geerling, Miranda Van Eck

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Background and aims: Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated.

Methods: The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined. Finally, susceptibility for atherosclerotic lesion formation was investigated in bone marrow-specific Prg4 knockout (KO) mice.

Results: Prg4 mRNA expression was induced 91-fold (p

Conclusions: Prg4 is present in macrophages in both murine and human atherosclerotic lesions and critically influences macrophage function, but deletion of Prg4 in bone marrow-derived cells does not affect atherosclerotic lesion development. (C) 2018 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalATHEROSCLEROSIS
Volume274
DOIs
Publication statusPublished - Jul-2018

Keywords

  • Proteoglycan 4
  • Proteoglycans
  • Macrophage function
  • Bone marrow transplantation
  • Atherosclerosis
  • HEPARAN-SULFATE PROTEOGLYCANS
  • RECEPTOR
  • CELLS
  • LIPOPROTEINS
  • METABOLISM
  • BIGLYCAN
  • VERSICAN
  • MICE
  • APOLIPOPROTEIN
  • PERLECAN

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