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• W2089533629 abstract "Because both endothelin-1 (ET-1) and angiotensin II (AngII) are independent mediators of arterial remodeling, we sought to determine the role of ET receptor inhibition in AngII-accelerated atherosclerosis and aortic aneurysm formation. We administered saline or AngII and/or bosentan, an endothelin receptor antagonist (ERA) for 7, 14, or 28 days to 6-week- and 6-month-old apolipoprotein E-knockout mice. AngII treatment increased aortic atherosclerosis, which was reduced by ERA. ET-1 immunostaining was localized to macrophage-rich regions in aneurysmal vessels. ERA did not prevent AngII-induced aneurysm formation but instead may have increased aneurysm incidence. In AngII-treated animals with aneurysms, ERA had a profound effect on the non-aneurysmal thoracic aorta via increasing wall thickness, collagen/elastin ratio, wall stiffness, and viscous responses. These observations were confirmed in acute in vitro collagen sheet production models in which ERA inhibited AngII's dose-dependent effect on collagen type 1 α 1 (COL1A1) gene transcription. However, chronic treatment reduced matrix metalloproteinase 2 mRNA expression but enhanced COL3A1, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 mRNA expressions. These data confirm a role for the ET system in AngII-accelerated atherosclerosis but suggest that ERA therapy is not protective against the formation of AngII-induced aneurysms and can paradoxically stimulate a chronic arterial matrix remodeling response." @default.
• W2089533629 created "2016-06-24" @default.
• W2089533629 creator A5055812329 @default.
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• W2089533629 creator A5079484780 @default.
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• W2089533629 date "2011-09-01" @default.
• W2089533629 modified "2023-09-29" @default.
• W2089533629 title "Differential Roles of Endothelin-1 in Angiotensin II-Induced Atherosclerosis and Aortic Aneurysms in Apolipoprotein E-Null Mice" @default.
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• W2089533629 doi "https://doi.org/10.1016/j.ajpath.2011.05.014" @default.
• W2089533629 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3157254" @default.
• W2089533629 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21718678" @default.
• W2089533629 hasPublicationYear "2011" @default.
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