Orecchioni, Marco ORCID: 0000-0002-3602-8510, Kobiyama, Kouji, Winkels, Holger ORCID: 0000-0003-1333-2031, Ghosheh, Yanal ORCID: 0000-0002-3733-2098, McArdle, Sara, Mikulski, Zbigniew ORCID: 0000-0002-1918-9216, Kiosses, William B., Fan, Zhichao ORCID: 0000-0001-5385-9626, Wen, Lai ORCID: 0000-0001-9760-3403, Jung, Yunmin ORCID: 0000-0002-4734-5837, Roy, Payel, Ali, Amal J., Miyamoto, Yukiko, Mangan, Matthew ORCID: 0000-0001-5990-3034, Makings, Jeffrey, Wang, Zhihao ORCID: 0000-0002-2597-4464, Denn, Angela, Vallejo, Jenifer, Owens, Michaela, Durant, Christopher P., Braumann, Simon, Mader, Navid, Li, Lin, Matsunami, Hiroaki, Eckmann, Lars, Latz, Eicke ORCID: 0000-0003-1488-5666, Wang, Zeneng, Hazen, Stanley L. and Ley, Klaus (2022). Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production. Science, 375 (6577). S. 214 - 418. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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Abstract

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-1b 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Orecchioni, MarcoUNSPECIFIEDorcid.org/0000-0002-3602-8510UNSPECIFIED
Kobiyama, KoujiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkels, HolgerUNSPECIFIEDorcid.org/0000-0003-1333-2031UNSPECIFIED
Ghosheh, YanalUNSPECIFIEDorcid.org/0000-0002-3733-2098UNSPECIFIED
McArdle, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mikulski, ZbigniewUNSPECIFIEDorcid.org/0000-0002-1918-9216UNSPECIFIED
Kiosses, William B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fan, ZhichaoUNSPECIFIEDorcid.org/0000-0001-5385-9626UNSPECIFIED
Wen, LaiUNSPECIFIEDorcid.org/0000-0001-9760-3403UNSPECIFIED
Jung, YunminUNSPECIFIEDorcid.org/0000-0002-4734-5837UNSPECIFIED
Roy, PayelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ali, Amal J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miyamoto, YukikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangan, MatthewUNSPECIFIEDorcid.org/0000-0001-5990-3034UNSPECIFIED
Makings, JeffreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, ZhihaoUNSPECIFIEDorcid.org/0000-0002-2597-4464UNSPECIFIED
Denn, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vallejo, JeniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owens, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durant, Christopher P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braumann, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mader, NavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, LinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matsunami, HiroakiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckmann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Latz, EickeUNSPECIFIEDorcid.org/0000-0003-1488-5666UNSPECIFIED
Wang, ZenengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hazen, Stanley L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ley, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-689745
DOI: 10.1126/science.abg3067
Journal or Publication Title: Science
Volume: 375
Number: 6577
Page Range: S. 214 - 418
Date: 2022
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1095-9203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SMOOTH-MUSCLE-CELLS; LIPID-PEROXIDATION; ODORANT RECEPTORS; OXIDIZED LDL; MOUSE; REPERTOIRE; ALDEHYDE; EXPRESSION; FAMILY; GENEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68974

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