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- W2279556601 abstract "Background: Transgenic mice with endothelium specific preproendothelin-1 overexpression (eET-1) exhibit endothelial dysfunction and vascular remodeling, oxidative stress and inflammation independently of hemodynamic effects. However, it is unclear whether vascular inflammation is causally implicated in adverse vascular effects of endothelin-1 (ET-1). We hypothesized that ET-1-induced vascular injury is decreased in a model of reduced macrophage-dependent inflammation, macrophage colony stimulating factor ( mCsf ) mice heterozygote for the osteopetrosis (Op) mutation. Methods and Results: Wild type (WT), eET-1, mCsf Op/+ and eET-1/ mCsf Op/+ mice were studied. There was no difference in tail-cuff 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/ mCsf Op/+ . However, in the presence of L-NAME, the magnitude of NO-independent relaxation was greater in eET-1/ mCsf Op/+ compared to eET-1 (72.4±6.7% vs. 40.8±14.4%, P <0.001). Media-to-lumen ratio was greater in eET-1 than WT (0.13±0.01 vs. 0.08±0.01, P <0.01) and unchanged in eET-1/ mCsf Op/+ (0.10±0.01). Media cross-sectional area (μm 2 ) was greater in eET-1 than WT (13521±2106 vs. 8112±381, P <0.05) and unchanged in eET-1/ mCsf Op/+ (8966±1125). Dihydroethidium staining revealed that reactive oxygen species production in aorta was 4-fold higher in eET-1 than WT ( P <0.01) and unchanged in eET-1/mCsf Op/+ . Aortic monocyte/macrophage infiltration was increased 2.6-fold in eET-1 ( P <0.01) and tended to decrease by 45% in eET-1/mCsf Op/+ compared to WT. Conclusion: Reduction of macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in improved vascular relaxation and reduced vascular remodeling, oxidative stress and inflammation, providing evidence for a role of macrophages and innate immunity in ET-1-induced vascular damage." @default.
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- W2279556601 date "2012-09-01" @default.
- W2279556601 modified "2023-09-27" @default.
- W2279556601 title "Abstract 60: Reduced Macrophage-dependent Inflammation Improves Endothelial Function and Vascular Remodeling, Oxidative Stress and Inflammation in a Model Of Endothelin-1 Induced Vascular Injury" @default.
- W2279556601 doi "https://doi.org/10.1161/hyp.60.suppl_1.a60" @default.
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