Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production.

Journal Article (Journal Article)

Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled chemoreceptors that have a central role in detecting odorants and the sense of smell. We found that mouse vascular macrophages express the olfactory receptor Olfr2 and all associated trafficking and signaling molecules. Olfr2 detects the compound octanal, which activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome and induces interleukin-1β secretion in human and mouse macrophages. We found that human and mouse blood plasma contains octanal, a product of lipid peroxidation, at concentrations sufficient to activate Olfr2 and the human ortholog olfactory receptor 6A2 (OR6A2). Boosting octanal levels exacerbated atherosclerosis, whereas genetic targeting of Olfr2 in mice significantly reduced atherosclerotic plaques. Our findings suggest that inhibiting OR6A2 may provide a promising strategy to prevent and treat atherosclerosis.

Full Text

Duke Authors

Cited Authors

  • Orecchioni, M; Kobiyama, K; Winkels, H; Ghosheh, Y; McArdle, S; Mikulski, Z; Kiosses, WB; Fan, Z; Wen, L; Jung, Y; Roy, P; Ali, AJ; Miyamoto, Y; Mangan, M; Makings, J; Wang, Z; Denn, A; Vallejo, J; Owens, M; Durant, CP; Braumann, S; Mader, N; Li, L; Matsunami, H; Eckmann, L; Latz, E; Wang, Z; Hazen, SL; Ley, K

Published Date

  • January 14, 2022

Published In

Volume / Issue

  • 375 / 6577

Start / End Page

  • 214 - 221

PubMed ID

  • 35025664

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.abg3067

Language

  • eng

Conference Location

  • United States