OR6A2, the human ortholog of mouse Olfr2, is an olfactory receptor belonging to the G-protein-coupled receptor family. It plays a role in detecting the compound octanal. When activated by octanal, it is involved in the NLRP3 inflammasome-dependent interleukin-1β (IL-1β) secretion pathway, which has implications in inflammatory responses [1].

In mouse models, genetic targeting of Olfr2 (the mouse ortholog of OR6A2) significantly reduced atherosclerotic plaques. Boosting octanal levels exacerbated atherosclerosis, indicating that activation of Olfr2/OR6A2 promotes the development of atherosclerosis [1]. This shows that in vivo, the function of OR6A2 (through its mouse ortholog) can influence the progression of atherosclerotic disease.

In conclusion, OR6A2 is an olfactory receptor that activates the NLRP3-IL-1β pathway upon octanal binding. Mouse models with genetic targeting of its ortholog Olfr2 have revealed its role in promoting atherosclerosis, suggesting that inhibiting OR6A2 could be a potential strategy for preventing and treating this disease [1].

References:

1. Orecchioni, Marco, Kobiyama, Kouji, Winkels, Holger, Hazen, Stanley L, Ley, Klaus. 2022. Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production. In Science (New York, N.Y.), 375, 214-221. doi:10.1126/science.abg3067. https://pubmed.ncbi.nlm.nih.gov/35025664/

2. Orecchioni, Marco, Matsunami, Hiroaki, Ley, Klaus. 2022. Olfactory receptors in macrophages and inflammation. In Frontiers in immunology, 13, 1029244. doi:10.3389/fimmu.2022.1029244. https://pubmed.ncbi.nlm.nih.gov/36311776/

3. Wang, Congcong, Andreasson, Katrin I. 2022. Odorant receptors in macrophages: potential targets for atherosclerosis. In Trends in immunology, 43, 262-264. doi:10.1016/j.it.2022.02.006. https://pubmed.ncbi.nlm.nih.gov/35283015/