The pro-fibrotic and anti-inflammatory foam cell macrophage paradox

Anita C Thomas, Wouter Eigelaar, Mat Daemen, Andrew C Newby

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

5 Citations (Scopus)
363 Downloads (Pure)

Abstract

The formation of foamy macrophages by sequestering extracellular modified lipids is a key event in atherosclerosis. However, there is controversy about the effects of lipid loading on macrophage phenotype, with in vitro evidence suggesting either pro- or anti-inflammatory consequences. To investigate this in vivo we compared the transcriptomes of foamy and non-foamy macrophages that accumulate in experimental subcutaneous granulomas in fat-fed ApoE null mice or normal chow-fed wild-type mice, respectively. Consistent with previous studies in peritoneal macrophages from LDL receptor null mice (Spann et al., 2012 [1]), we found that anti-inflammatory LXR/RXR pathway genes were over-represented in the foamy macrophages, but there was no change in M1 or M2 phenotypic markers. Quite unexpectedly, however, we found that genes related to the induction of fibrosis had also been up-regulated (Thomas et al., 2015 [2]). The progression of the foamy macrophages along anti-inflammatory and pro-fibrotic pathways was confirmed using immunohistochemistry (described fully in our primary research article (Thomas et al., 2015 [2]). Here we provide additional details on production of the macrophages and their transcriptomic comparison,with the rawand processed microarray data deposited in GEO (accession number GSE70126). Our observations on these cells are indeed paradoxical, because foamy macrophages have long been implicated in promoting inflammation, extracellular matrix degradation and atherosclerotic plaque rupture, which must be provoked by additional local mediators. Our findings probably explain how very early macrophage-rich lesions maintain their structural integrity.
Original languageEnglish
Pages (from-to)136-138
Number of pages3
JournalGenomics Data
Volume6
Early online date10 Sep 2015
DOIs
Publication statusPublished - Dec 2015

Bibliographical note

Date of Acceptance: 27/08/2015

Keywords

  • Foam cell macrophage
  • Atherosclerosis
  • Inflammation
  • Fibrosis
  • Non-foamy macrophage

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