{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:50:39Z","timestamp":1792464639919,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T00:00:00Z","timestamp":1487030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["086867\/Z\/08\/Z"],"award-info":[{"award-number":["086867\/Z\/08\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["20140222"],"award-info":[{"award-number":["20140222"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2014\u20102312"],"award-info":[{"award-number":["2014\u20102312"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Atherosclerosis is characterized by a chronic non\u2010resolving inflammation in the arterial wall. Aspirin\u2010triggered lipoxin A4 (ATL) is a potent anti\u2010inflammatory mediator, involved in the resolution of inflammation. However, the therapeutic potential of immune targeting by means of ATL in atherosclerosis has not previously been explored. The aim of the present study was to determine the effects of ATL and its receptor Fpr2 on atherosclerosis development and progression in apolipoprotein E deficient (ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\u00a0\u00d7\u00a0Fpr2<jats:sup>+\/+<\/jats:sup> and ApoE<jats:sup>\u2212\/\u2212<\/jats:sup>\u00a0\u00d7\u00a0Fpr2<jats:sup>\u2212\/\u2212<\/jats:sup> mice were generated. Four\u2010week\u2010old mice fed a high\u2010fat diet for 4\u00a0weeks and 16\u2010week\u2010old mice fed chow diet received osmotic pumps containing either vehicle or ATL for 4\u00a0weeks. Atherosclerotic lesion size and cellular composition were measured in the aortic root and thoracic aorta. Lipid levels and leukocyte counts were measured in blood and mRNA was isolated from abdominal aorta and spleen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>ATL blocked atherosclerosis progression in the aortic root and thoracic aorta of ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In addition, ATL reduced macrophage infiltration and apoptotic cells in atherosclerotic lesions. The mRNA levels of several cytokines and chemokines in the spleen and aorta were reduced by ATL, whereas circulating leukocyte levels were unchanged. The ATL\u2010induced athero\u2010protection was absent in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice lacking the Fpr2 receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>ATL blocked atherosclerosis progression by means of an Fpr2\u2010mediated reduced local and systemic inflammation. These results suggest this anti\u2010inflammatory and pro\u2010resolving agent has therapeutic potential for the treatment of atherosclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v174.22\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v174.22\/issuetoc<\/jats:ext-link> and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcp.v82.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcp.v82.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13707","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T11:42:46Z","timestamp":1484048566000},"page":"4043-4054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Aspirin\u2010triggered lipoxin A4 inhibits atherosclerosis progression in apolipoprotein E<sup>\u2212\/\u2212<\/sup> mice"],"prefix":"10.1111","volume":"174","author":[{"given":"Marcelo H","family":"Petri","sequence":"first","affiliation":[{"name":"Experimental Cardiovascular Research Group, Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Laguna\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Experimental Cardiovascular Research Group, Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildur","family":"Arnardottir","sequence":"additional","affiliation":[{"name":"Experimental Cardiovascular Research Group, Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig E","family":"Wheelock","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karlinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran K","family":"Hansson","sequence":"additional","affiliation":[{"name":"Experimental Cardiovascular Research Group, Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"B\u00e4ck","sequence":"additional","affiliation":[{"name":"Experimental Cardiovascular Research Group, Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Cardiology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505845102"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12665"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004812"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-496661"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.86.1.56"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00024.2014"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0770com"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305825"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903526"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa1065"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.1663"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3099"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091082"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.11.052"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","unstructured":"KetelhuthDF HermanssonA HlawatyH LetourneurD YanZQ &BackM(2015).The leukotriene B receptor (BLT) antagonist BIIL284 decreases atherosclerosis in ApoE mice. Prostaglandins & other lipid mediators.","DOI":"10.1016\/j.prostaglandins.2015.05.007"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.01.028"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10146"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-159913"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu224"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.11.010"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(97)00001-4"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13479"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-263160"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P022814"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.167197"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2205"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.224873"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020633"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.04.013"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001578"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T12:27:46Z","timestamp":1695990466000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,14]]},"references-count":36,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/bph.13707"],"URL":"https:\/\/doi.org\/10.1111\/bph.13707","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,14]]},"assertion":[{"value":"2016-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}