{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:19:22Z","timestamp":1790601562514,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2011\/03\/N\/NZ4\/03760"],"award-info":[{"award-number":["2011\/03\/N\/NZ4\/03760"]}],"id":[{"id":"10.13039\/501100004281","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>Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1\u20137 (Ang\u2010(1\u20137)) in vascular pathologies suggested the therapeutic use of low MW, non\u2010peptide Ang\u2010(1\u20137) mimetics, such as AVE0991. The mechanisms underlying the vaso\u2010protective effects of AVE0991, a Mas receptor agonist, remain to be explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)\u2212\/\u2212 mice, in the context of vascular inflammation and plaque stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>AVE0991 has significant anti\u2010atherosclerotic properties in ApoE\u2212\/\u2212 mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow\u2010fed ApoE\u2212\/\u2212 mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T\u2010cells precedes atherosclerotic plaque or the impairment of endothelium\u2010dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes\/macrophages inhibiting their activation, characterized by production of IL\u20101\u03b2, TNF\u2010\u03b1, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP\u20101 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP\u20101 cells <jats:italic>in vitro<\/jats:italic>, and the anti\u2010inflammatory effects of AVE0991 were partly Mas dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The selective Mas receptor agonist AVE0991 exhibited anti\u2010atherosclerotic and anti\u2010inflammatory actions, affecting monocyte\/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoE\u2212\/\u2212 mice.<\/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.13685","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T13:10:10Z","timestamp":1481289010000},"page":"4055-4069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Anti\u2010atherosclerotic effect of the angiotensin 1\u20137 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis"],"prefix":"10.1111","volume":"174","author":[{"given":"D S","family":"Skiba","sequence":"first","affiliation":[{"name":"Department of Internal and Agricultural Medicine Jagiellonian University School of Medicine  Krakow Poland"},{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Nosalski","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine Jagiellonian University School of Medicine  Krakow Poland"},{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T P","family":"Mikolajczyk","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine Jagiellonian University School of Medicine  Krakow Poland"},{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  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