دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Platelet olfactory receptor activation limits platelet reactivity and growth of aortic aneurysms.
المؤلفون: Morrell CN; Aab Cardiovascular Research Institute, Department of Medicine, Microbiology and Immunology, and Laboratory Medicine and., Mix D; Department of Surgery, Division of Vascular Surgery, University of Rochester School of Medicine, New York, New York, USA., Aggarwal A; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA., Bhandari R; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA., Godwin M; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA., Owens P 3rd; Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Lyden SP; Heart, Vascular and Thoracic Institute, Department of Vascular Surgery, Cleveland, Ohio, USA., Doyle A; Department of Surgery, Division of Vascular Surgery, University of Rochester School of Medicine, New York, New York, USA., Krauel K; Departments of Internal Medicine and Pathology and the Molecular Medicine Program at the University of Utah Health Sciences Center, Eccles Institute of Human Genetics, Salt Lake City, Utah, USA.; Department of Internal Medicine and GRECC at the George E. Wahlen VAMC, Salt Lake City, Utah, USA.; Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA.; Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany., Rondina MT; Departments of Internal Medicine and Pathology and the Molecular Medicine Program at the University of Utah Health Sciences Center, Eccles Institute of Human Genetics, Salt Lake City, Utah, USA.; Department of Internal Medicine and GRECC at the George E. Wahlen VAMC, Salt Lake City, Utah, USA.; Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA., Mohan A; Aab Cardiovascular Research Institute, Department of Medicine, Microbiology and Immunology, and Laboratory Medicine and., Lowenstein CJ; Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Shim S; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA., Stauffer S; Cleveland Clinic Center for Therapeutics Discovery, Lerner Research Institute, Cleveland, Ohio, USA., Josyula VP; Cleveland Clinic Center for Therapeutics Discovery, Lerner Research Institute, Cleveland, Ohio, USA., Ture SK; Aab Cardiovascular Research Institute, Department of Medicine, Microbiology and Immunology, and Laboratory Medicine and., Yule DI; Department of Pharmacology and Physiology and., Wagner LE 3rd; Department of Pharmacology and Physiology and., Ashton JM; Department of Biomedical Genetics, University of Rochester School of Medicine, Rochester, New York, USA., Elbadawi A; Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, Texas, USA., Cameron SJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA.; Heart Vascular and Thoracic Institute, Department of Cardiovascular Medicine, Section of Vascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA.; Case Western Reserve University Lerner College of Medicine, Cleveland, Ohio, USA.; Department of Hematology, Taussig Cancer Center, Cleveland, Ohio, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2022 May 02; Vol. 132 (9).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Aortic Aneurysm*/genetics , Aortic Aneurysm*/metabolism , Aortic Aneurysm, Abdominal*/genetics , Receptors, Odorant*/genetics, Animals ; Blood Platelets/metabolism ; Disease Models, Animal ; Humans ; Mice ; Platelet Activation ; Platelet Aggregation Inhibitors/therapeutic use
مستخلص: 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.
References: Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4410-5. (PMID: 23401498)
Nat Mater. 2019 Jul;18(7):760-769. (PMID: 30911119)
Proteomics. 2017 Mar;17(6):. (PMID: 27452734)
Genomics. 2013 Jun;101(6):313-7. (PMID: 23462555)
Cardiovasc Diagn Ther. 2018 Oct;8(5):610-620. (PMID: 30498685)
J Vasc Surg. 2018 Apr;67(4):1051-1058.e1. (PMID: 29141786)
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2584-9. (PMID: 14983052)
Circulation. 2015 Jul 7;132(1):47-58. (PMID: 25934838)
J Clin Invest. 2017 Nov 1;127(11):4118-4123. (PMID: 28990936)
Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2700-2713. (PMID: 32907367)
J Vasc Surg. 1996 Jul;24(1):127-33. (PMID: 8691515)
J Exp Med. 2008 Mar 17;205(3):575-84. (PMID: 18283118)
J Cell Biol. 2011 May 30;193(5):867-84. (PMID: 21624955)
Sci Rep. 2018 Jul 13;8(1):10600. (PMID: 30006552)
J Biol Chem. 2012 Jun 22;287(26):22287-94. (PMID: 22570474)
Cardiovasc Res. 2020 Feb 1;116(2):450-456. (PMID: 31135888)
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):390-400. (PMID: 33176447)
J Thromb Haemost. 2009 Feb;7(2):241-6. (PMID: 18983498)
Eur J Vasc Endovasc Surg. 2003 Jan;25(1):16-22. (PMID: 12525806)
Blood. 2020 Sep 10;136(11):1330-1341. (PMID: 32678428)
Nat Commun. 2020 May 4;11(1):2188. (PMID: 32366818)
J Intern Med. 2021 Aug;290(2):451-461. (PMID: 33403772)
Experientia. 1975 May 15;31(5):530. (PMID: 1140245)
Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2460-2467. (PMID: 27687605)
Vascul Pharmacol. 2021 Feb;136:106818. (PMID: 33227452)
Acta Pharmacol Sin. 2011 Jun;32(6):685-92. (PMID: 21642943)
Cell. 2018 Jul 26;174(3):636-648.e18. (PMID: 30017246)
Blood. 2020 Sep 10;136(11):1317-1329. (PMID: 32573711)
Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28485-28495. (PMID: 33097666)
Circulation. 2013 May 21;127(20):2031-7. (PMID: 23599348)
J Am Coll Cardiol. 2020 Apr 7;75(13):1609-1610. (PMID: 32241378)
Circ Res. 2003 May 2;92(8):827-39. (PMID: 12730128)
Nature. 1966 Feb 5;209(5023):571-2. (PMID: 5921179)
JACC Basic Transl Sci. 2021 Dec 08;7(1):14-25. (PMID: 35128205)
Curr Med Chem. 2010;17(26):2897-905. (PMID: 20858171)
Thromb Haemost. 1997 Apr;77(4):748-54. (PMID: 9134654)
J Vasc Surg. 2017 Aug;66(2):396-403. (PMID: 28190712)
eNeuro. 2017 Oct 31;4(5):. (PMID: 29094064)
Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):1594-1606. (PMID: 29724818)
Exp Hematol. 2009 Jul;37(7):849-56. (PMID: 19410025)
J Biomech Eng. 2015 Apr;137(4):041005. (PMID: 25588057)
J Pharmacol Exp Ther. 2019 May;369(2):182-187. (PMID: 30765424)
Lancet. 1986 Jul 19;2(8499):166. (PMID: 2873430)
Blood. 2018 Dec 20;132(25):2619-2628. (PMID: 30228233)
Arterioscler Thromb Vasc Biol. 2015 Sep;35(9):2032-2041. (PMID: 26139462)
Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):2171-2181. (PMID: 28912363)
Sci Rep. 2018 Sep 5;8(1):13273. (PMID: 30185838)
Nature. 2001 Jan 11;409(6817):202-7. (PMID: 11196645)
معلومات مُعتمدة: L30 HL120200 United States HL NHLBI NIH HHS; R01 HL158801 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Platelets; Signal transduction; Thrombosis; Vascular Biology
المشرفين على المادة: 0 (Platelet Aggregation Inhibitors)
0 (Receptors, Odorant)
تواريخ الأحداث: Date Created: 20220324 Date Completed: 20220503 Latest Revision: 20220728
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9057618
DOI: 10.1172/JCI152373
PMID: 35324479
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI152373