Platelet olfactory receptor activation limits platelet reactivity and growth of aortic aneurysms

Abstract: As blood transitions from steady laminar flow (S-flow) in healthy arteries to disturbed flow (D-flow) in aneurysmal arteries, platelets are subjected to external forces. Biomechanical platelet activation is incompletely understood and is a potential mechanism behind antiplatelet medication resistance. Although it has been demonstrated that antiplatelet drugs suppress the growth of abdominal aortic aneurysms (AAA) in patients, we found that a certain degree of platelet reactivity persisted in spite of aspirin therapy, urging us to consider additional antiplatelet therapeutic targets. Transcriptomic profiling of platelets from patients with AAA revealed upregulation of a signal transduction pathway common to olfactory receptors, and this was explored as a mediator of AAA progression. Healthy platelets subjected to D-flow ex vivo, platelets from patients with AAA, and platelets in murine models of AAA demonstrated increased membrane olfactory receptor 2L13 (OR2L13) expression. A drug screen identified a molecule activating platelet OR2L13, which limited both biochemical and biomechanical platelet activation as well as AAA growth. This observation was further supported by selective deletion of the OR2L13 ortholog in a murine model of AAA that accelerated aortic aneurysm growth and rupture. These studies revealed that olfactory receptors regulate platelet activation in AAA and aneurysmal progression through platelet-derived mediators of aortic remodeling

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: The journal of clinical investigation. - 132, 9 (2022) , e152373, ISSN: 1558-8238

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2022
• Urheber: Morrell, Craig N ; Mix, Doran ; Aggarwal, Anu ; Bhandari, Rohan ; Godwin, Matthew ; Owens, Phillip ; Lyden, Sean P. ; Doyle, Adam ; Krauel, Krystin ; Rondina, Matthew T. ; Mohan, Amy ; Lowenstein, Charles J. ; Shim, Sharon ; Stauffer, Shaun ; Josyula, Vara Prasad ; Ture, Sara K. ; Yule, David I. ; Wagner, Larry E. ; Ashton, John M. ; Elbadawi, Ayman ; Cameron, Scott J.

Weitere Informationen

• DOI: 10.1172/JCI152373
• URN: urn:nbn:de:bsz:25-freidok-2277502
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:58 MESZ