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

Thomas AC, Eijgelaar WJ, Daemen MJ, Newby AC - Genom Data (2015)

Bottom Line: 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]).Our findings probably explain how very early macrophage-rich lesions maintain their structural integrity.

View Article: PubMed Central - PubMed

Affiliation: Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.

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 mice or normal chow-fed wild-type mice, respectively. Consistent with previous studies in peritoneal macrophages from LDL receptor 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 raw and 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.

No MeSH data available.


Related in: MedlinePlus

Representation of macrophage production in mice. Foam cell macrophages (FCM) or non-foamy macrophages (NFM) were obtained from subcutaneous sponges inserted into mice. RNA was harvested from isolated macrophages and further samples were taken for examination using immunocytochemistry (ICC) or immunohistochemistry (IHC).
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f0005: Representation of macrophage production in mice. Foam cell macrophages (FCM) or non-foamy macrophages (NFM) were obtained from subcutaneous sponges inserted into mice. RNA was harvested from isolated macrophages and further samples were taken for examination using immunocytochemistry (ICC) or immunohistochemistry (IHC).

Mentions: The housing and care of all animals and procedures used in these studies was in accordance with and under licence of the Animals (Scientific Procedures) Act 1986 (London, United Kingdom), which transposes EU Directive 2010/63/EU. We obtained homozygous ApoE−/− and ApoE+/+ mice on a C57/BL background from University of Bristol colonies. Animals were housed conventionally, and were given food and water ad libitum throughout the experiments. Animals were treated as outlined in Fig. 1.


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

Thomas AC, Eijgelaar WJ, Daemen MJ, Newby AC - Genom Data (2015)

Representation of macrophage production in mice. Foam cell macrophages (FCM) or non-foamy macrophages (NFM) were obtained from subcutaneous sponges inserted into mice. RNA was harvested from isolated macrophages and further samples were taken for examination using immunocytochemistry (ICC) or immunohistochemistry (IHC).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664709&req=5

f0005: Representation of macrophage production in mice. Foam cell macrophages (FCM) or non-foamy macrophages (NFM) were obtained from subcutaneous sponges inserted into mice. RNA was harvested from isolated macrophages and further samples were taken for examination using immunocytochemistry (ICC) or immunohistochemistry (IHC).
Mentions: The housing and care of all animals and procedures used in these studies was in accordance with and under licence of the Animals (Scientific Procedures) Act 1986 (London, United Kingdom), which transposes EU Directive 2010/63/EU. We obtained homozygous ApoE−/− and ApoE+/+ mice on a C57/BL background from University of Bristol colonies. Animals were housed conventionally, and were given food and water ad libitum throughout the experiments. Animals were treated as outlined in Fig. 1.

Bottom Line: 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]).Our findings probably explain how very early macrophage-rich lesions maintain their structural integrity.

View Article: PubMed Central - PubMed

Affiliation: Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.

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 mice or normal chow-fed wild-type mice, respectively. Consistent with previous studies in peritoneal macrophages from LDL receptor 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 raw and 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.

No MeSH data available.


Related in: MedlinePlus