Wnt pathway activation, cell migration, and lipid uptake is regulated by low-density lipoprotein receptor-related protein 5 in human macrophages

Maria Borrell-Pags, July Carolina Romero, Oriol Juan-Babot, Lina Badimon

Research output: Contribution to journalArticlepeer-review

Abstract

Aims Atherosclerosis plaque development includes infiltration of inflammatory cells, accumulation of lipids and fibrous cap formation. Low-density lipoprotein receptor-related protein 1 (LRP1) is expressed on atherosclerotic lesions associated with macrophages and vascular smooth muscle cells. The aim of this work is to analyse the role in atherosclerosis lesion progression of another member of the LDL receptor protein family, low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor with Frizzled known to activate the Wnt signalling pathway in several cell types. Methods and resultsLRP5 is expressed in human vascular and innate inflammatory cells. LRP5 is transcriptionally regulated by aggregated LDL (agLDL), participating in the lipid uptake and transformation of macrophages into foam cells, a critical step in atherosclerosis progression. AgLDL-treated macrophages show up-regulated expression of β-catenin, LEF1, c-jun, cyclinD1, bone morphogenetic protein 2 (BMP2), and osteopontin (OPN), proteins and targets of the Wnt signalling pathway, whereas LRP5-silenced macrophages show a significant down-regulation of OPN and BMP2 expression. Furthermore, LRP5-deficient macrophages exhibit an impaired migration both in wound-repair and modified Boyden chambers models. ConclusionThese results demonstrate the involvement of LRP5 in the innate inflammatory reaction to lipid infiltration in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)2841-2850
Number of pages10
JournalEuropean heart journal
Volume32
Issue number22
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Atherosclerosis
  • Human macrophages
  • LRP5
  • Lipid uptake
  • Wnt signalling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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