G2A deficiency in mice promotes macrophage activation and atherosclerosis

David T. Bolick, Marcus D. Skaflen, Laura E. Johnson, Seong Chun Kwon, Deborah Howatt, Alan Daugherty, Kodi S. Ravichandran, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


G2A is a stress-inducible G protein-coupled receptor that is expressed on several cell types within atherosclerotic lesions. We demonstrated previously that G2A deficiency in mice increased aortic monocyte recruitment and increased monocyte:endothelial interactions. To investigate the impact of G2A deficiency in macrophages, we isolated peritoneal macrophages from G2A +/+ApoE -/-and G2A -/-ApoE -/- mice. G2A -/-ApoE -/- macrophages had significantly lower apoptosis than control macrophages. The prosurvival genes BCL-2, BCL-xL, and cFLIP were increased in G2AApoE macrophages. Macrophages from G2AApoE mice also had increased proinflammatory status that was indicative of a M1 macrophage phenotype. This was indicated by significantly increased nuclear translocation of nuclear factor κB, as well as production of interleukin-12p40, tumor necrosis factor α, and interleukin-6, and reduced expression of arginase-I. Moreover, G2A -/-ApoE -/- macrophages had reduced ability to engulf apoptotic cells in vitro. We examined atherosclerosis in mice fed a Western diet for 10 weeks and found that G2A deficiency increased lesion size in the aortic root by 50%. Plasma lipid levels were not changed in G2AApoE mice. However, we found that absence of G2A increased the number of aortic macrophages and attenuated apoptosis in this cell type. Moreover, bone marrow transplantation studies indicated that deficiency of G2A in marrow-derived cells significantly contributed to atherosclerosis evelopment. In the absence of G2A, increased macrophage activation and decreased apoptosis is associated with accumulation of macrophages in the aorta and increased atherosclerosis.

Original languageEnglish
Pages (from-to)318-327
Number of pages10
JournalCirculation Research
Issue number3
StatePublished - Feb 13 2009


  • Apoptosis
  • Atherosclerosis
  • Macrophages
  • Vascular inflammation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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