{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:35:36Z","timestamp":1790868936459,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T00:00:00Z","timestamp":1483488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006366","name":"Minist\u00e9rio da Educa\u00e7\u00e3o","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_152639\/1"],"award-info":[{"award-number":["310030_152639\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neutrophil\u2010mediated inflammation was recently identified as an active contributor to athero\u2010progression. Therapeutic strategies inhibiting neutrophil degranulation or recruitment were hypothesized to positively impact on plaque vulnerability. In this study, we investigated whether treatment with the recently discovered agonist of the Mas\u2010related G\u2010coupled receptor type D (MrgD) alamandine would impact on neutrophil degranulation <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Fifteen\u2010week\u2010old ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice were fed with a Western\u2010type diet for an additional 11 weeks. After the first 2 weeks of diet, mice were surgically implanted with a carotid \u2018cast\u2019 device that alters the blood shear stress and induces different carotid plaque phenotypes. During the last 4 weeks before euthanasia, mice were randomly assigned to subcutaneously receive vehicle (NaCl 0\u00b715 M) or alamandine (24 \u03bcg\/kg\/h) by micropump. For <jats:italic>in vitro<\/jats:italic> experiments, neutrophils were obtained after thioglycollate intraperitoneal injection in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with alamandine was well\u2010tolerated, but failed to affect lipid, macrophage, neutrophil or collagen content within carotid and aortic root plaques. Also, treatment with alamandine did not affect Th\u2010cell polarization in lymphoid organs. Conversely, alamandine administration was associated with a reduction in serum levels of neutrophil granule enzymes, such as MMP\u20109 and MPO as well as MMP\u20109 content within aortic root plaques. <jats:italic>In vitro<\/jats:italic>, preincubation with alamandine dose\u2010dependently abrogated PMA\u2010induced neutrophil degranulation of MMP\u20109 and MPO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that treatment with the MrgD agonist alamandine led to a reduced release of neutrophil granule products, potentially interfering with pro\u2010atherosclerotic neutrophil activation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12708","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T21:46:39Z","timestamp":1481233599000},"page":"117-128","source":"Crossref","is-referenced-by-count":22,"title":["Alamandine abrogates neutrophil degranulation in atherosclerotic mice"],"prefix":"10.1111","volume":"47","author":[{"given":"Analina R.","family":"Da Silva","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medical Specialties Foundation for Medical Researches University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Lenglet","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medical Specialties Foundation for Medical Researches University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-4078","authenticated-orcid":false,"given":"Federico","family":"Carbone","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine Department of Internal Medicine University of Genoa School of Medicine Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Burger","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medical Specialties Foundation for Medical Researches University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Roth","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medical Specialties Foundation for Medical Researches University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Liberale","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine Department of Internal Medicine University of Genoa School of Medicine Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Bonaventura","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine Department of Internal Medicine University of Genoa School of Medicine Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Dallegri","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine Department of Internal Medicine University of Genoa School of Medicine Genoa Italy"},{"name":"IRCCS AOU San Martino \u2013 IST Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Stergiopulos","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson A. S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Mach","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medical Specialties Foundation for Medical Researches University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo A.","family":"Fraga\u2010Silva","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine Department of Internal Medicine University of Genoa School of Medicine Genoa Italy"},{"name":"IRCCS AOU San Martino \u2013 IST Genoa Italy"},{"name":"Centre of Excellence for Biomedical Research (CEBR) University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450115666141110093013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-03-0211"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-07-0531"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303564"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-02-0139"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.578369"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.008589"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/659282"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300275"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.097097"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-06-0448"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12401"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301077"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr449"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.590018"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.198"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.03.013"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2015.07.013"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00360.2012"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31828a6688"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.11.028"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148273"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-012-0242-3"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Feci.12708","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.12708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T21:09:31Z","timestamp":1696367371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.12708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,4]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1111\/eci.12708"],"URL":"https:\/\/doi.org\/10.1111\/eci.12708","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,4]]}}}