Foam cell formation in vivo converts macrophages to a pro-fibrotic phenotype

Anita Thomas, Wouter Eijgelaar, MJAP Daemen, Andrew Newby

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)
406 Downloads (Pure)

Abstract

Formation of foam cell macrophages, which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages.
Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-β action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and
fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques.
Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-β family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells.
Original languageEnglish
Article numbere0128163
Number of pages27
JournalPLoS ONE
Volume10
Issue number7
DOIs
Publication statusPublished - 31 Jul 2015

Bibliographical note

Date of Acceptance: 22/04/2015

Keywords

  • foam cell macrophage
  • plaque rupture
  • transforming growth factor-b
  • Fibrosis
  • Connective Tissue Growth Factor
  • Smad2
  • Macrophage Activation
  • macrophage polarization
  • LXR
  • cFOS
  • matrix metalloproteinase

Fingerprint Dive into the research topics of 'Foam cell formation in vivo converts macrophages to a pro-fibrotic phenotype'. Together they form a unique fingerprint.

Cite this