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• W2129872364 abstract "Transgenic mice with endothelium-specific endothelin-1 (ET-1) overexpression exhibit endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. We previously observed that monocytes/macrophages play a role in angiotensin II, aldosterone, and deoxycorticosterone acetate/salt-induced vascular remodeling, oxidative stress, and inflammation using a model with reduced monocytes/macrophages, the osteopetrotic (Op) mouse, which has a mutation in the macrophage colony stimulating factor ( Csf1 ) gene. However, it is unknown whether monocytes/macrophages are implicated in adverse vascular effects of ET-1. We hypothesized that reduction in monocytes/macrophages would blunt ET-1–induced vascular injury. We performed a study on 4- to 6-month-old male mice with endothelium-specific ET-1 overexpression (eET-1), reduction in CSF1 ( Csf1 Op/+ ), or both (eET-1/ Csf1 Op/+ ), and their wild-type littermate control mice. There was no difference in systolic blood pressure between groups. Endothelial function and vascular structure were determined on a pressurized myograph. Endothelium-dependent relaxation in response to acetylcholine was similar in eET-1 and eET-1/ Csf1 Op/+ mice. Media:lumen ratio and media cross-sectional area were ≈1.5-fold greater in eET-1 than in wild-type mice ( P <0.05), which was not observed in mice deficient in CSF1. ET-1–induced oxidative stress measured by dihydroethidium staining ( P <0.05) and NADPH oxidase activity assessed with lucigenin chemiluminescence ( P <0.05) were blunted by CSF1 deficiency. ET-1 caused a 2.5-fold increase in monocyte/macrophage infiltration compared with wild-type mice ( P <0.001), which was blunted in the mice deficient in CSF1. Reduction of monocyte/macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in reduced vascular remodeling and oxidative stress, providing evidence for a role of monocytes/macrophages and innate immunity in ET-1–induced vascular injury." @default.
• W2129872364 created "2016-06-24" @default.
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• W2129872364 date "2013-07-01" @default.
• W2129872364 modified "2023-10-16" @default.
• W2129872364 title "Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury" @default.
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• W2129872364 doi "https://doi.org/10.1161/hypertensionaha.113.01298" @default.
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