{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:22:46Z","timestamp":1793164966875,"version":"4.5.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Abdominal aortic aneurysms (AAAs) are characterized by ECM (extracellular matrix) degradation and chronic vascular inflammation, with macrophages playing a key role. The mechanisms regulating macrophage activation in AAA remain incompletely understood. Vascular macrophages express Olfr2 (olfactory receptor 2), a GPCR (G-protein\u2013coupled receptor) implicated in inflammation, but its role in AAA development is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We investigated the role of Olfr2 in AAA using PPE (porcine pancreatic elastase) infusion in Olfr2-deficient (\n                      <jats:italic toggle=\"yes\">Olfr2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      ), Ang II (angiotensin II) infusion in\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic toggle=\"yes\">Olfr2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice, bone marrow transplantation, and pharmacological modulation experiments. Echocardiography and histology were complemented by spectral flow cytometry, transcriptional profiling, and functional in vivo and ex vivo assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Microarray analysis revealed increased expression of the human\n                      <jats:italic toggle=\"yes\">Olfr2<\/jats:italic>\n                      orthologue\n                      <jats:italic toggle=\"yes\">OR6A2<\/jats:italic>\n                      (olfactory receptor family 6 subfamily A member 2) in AAA tissue. Flow cytometry showed OR6A2 upregulation in monocytes from patients with large versus small AAAs. In both human and murine tissues, up to 30% of vascular macrophages expressed OR6A2\/Olfr2, which peaked in MHCII\n                      <jats:sup>high<\/jats:sup>\n                      CCR2\n                      <jats:sup>low<\/jats:sup>\n                      monocytes\/macrophages on day 7 of experimental AAA. Both whole-body and hematopoietic Olfr2 deficiency protected mice from AAA formation, with reduced ECM degradation, decreased macrophage infiltration, and preserved smooth muscle cell content. Treatment with the Olfr2 agonist octanal exacerbated, while the antagonist citral reduced AAA and inflammation. In\n                      <jats:italic toggle=\"yes\">Olfr2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice, inflammatory gene expression and aortic leukocyte accumulation were diminished. Despite a similar total leukocyte count, Ly6C\n                      <jats:sup>high<\/jats:sup>\n                      monocytes displayed reduced CX3CR1 (CX3C motif chemokine receptor 1) expression and impaired migration toward CX3CL1 in vitro. Competitive transfer confirmed reduced migratory capacity of\n                      <jats:italic toggle=\"yes\">Olfr2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      monocytes, while pharmacological CX3CR1 inhibition mitigated the proinflammatory effects of octanal in AAA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Olfr2 regulates monocyte recruitment and macrophage-driven inflammation during AAA. Its genetic deletion or pharmacological inhibition protects against AAA, whereas receptor activation worsens the disease. Olfr2 represents a critical modulator of vascular inflammation and a potential therapeutic target in AAA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.326591","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:00:15Z","timestamp":1767175215000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Olfr2 Promotes Recruitment of Monocytes via CX3CR1 in Abdominal Aortic Aneurysm"],"prefix":"10.1161","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5532-5265","authenticated-orcid":true,"given":"Patrik","family":"Schelemei","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix S.R.","family":"Picard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8701-9888","authenticated-orcid":true,"given":"Yein","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-546X","authenticated-orcid":true,"given":"Philipp","family":"Wollnitzke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine III, (P.W., B.L.), Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-181X","authenticated-orcid":true,"given":"Harshal","family":"Nemade","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2980-0746","authenticated-orcid":true,"given":"Sebastian K.","family":"Lechner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-0290","authenticated-orcid":true,"given":"Dennis","family":"Mehrkens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Arkenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C.","family":"K\u00f6bele","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-3413","authenticated-orcid":true,"given":"Jan","family":"Wrobel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-6982","authenticated-orcid":true,"given":"Kristel","family":"Martinez Lagunas","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-671X","authenticated-orcid":true,"given":"Elena","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0979-1190","authenticated-orcid":true,"given":"Henning","family":"Guthoff","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-8892","authenticated-orcid":true,"given":"Alexander","family":"Hof","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., M.K., A.M.H., G.S., S.B., M.M., H.W.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany."},{"name":"Center for Cardiovascular Medicine Aachen-Bonn-Cologne-D\u00fcsseldorf, Germany (P.S., F.S.R.P., Y.P., H.N., S.K.L., D.M., P.A., A.C.K., J.W., K.M.L., E.W., H.G., A.H., T.R., S.B., M.M., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9226-6435","authenticated-orcid":true,"given":"Khalia","family":"Cummings","sequence":"additional","affiliation":[{"name":"Immunology Center of Georgia, Augusta University, Augusta, GA (K.C., M.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-3121","authenticated-orcid":true,"given":"Muntadher","family":"Al Zaidi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Cardiology, University Hospital Bonn, Bonn, Germany (M.A.Z., S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-2088","authenticated-orcid":true,"given":"Sebastian","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II-Cardiology, University Hospital Bonn, Bonn, Germany (M.A.Z., S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5645-1260","authenticated-orcid":true,"given":"Joy","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (J.R., M.L.L.)."},{"name":"Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden (J.R., M.L.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6821-6674","authenticated-orcid":true,"given":"Moritz","family":"Lindquist Liljeqvist","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (J.R., M.L.L.)."},{"name":"Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden (J.R., 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