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• W2100057322 abstract "Ebastine is a well-known selective second-generation histamine H(1) receptor antagonist, which is used for seasonal and perennial allergic rhinitis and chronic urticaria. Angiogenesis plays a crucial role in the development of airway inflammation and remodelling in allergic rhinitis and asthmatic patients, in whom, indeed, the mucosa displays increased vascularity and overexpression of vascular endothelial growth factor (VEGF). The aim of the present study was to evaluate the anti-angiogenic properties of carebastine, the active metabolite of ebastine. The effects of carebastine on human umbilical vein endothelial cell (EC) (HUVEC) and human pulmonary artery EC (HPAEC) proliferation, migration and capillary-like tube formation were investigated in vitro, and in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Moreover, the effect of carebastine on phosphorylation of the cell VEGF receptor fetal liver kinase-1, or VEGF receptor 2 (VEGFR-2), and Akt kinase (Akt) was evaluated by Western blotting. Carebastine inhibited VEGF-induced HUVEC and HPAEC proliferation, migration and angiogenesis in a dose-dependent manner in vitro. Cell proliferation was inhibited by 42 and 64% in HUVECs and 62 and 75% in HPAECs upon exposure for 48 and 72 h, respectively, to 20 microM carebastine (p < or = 0.03), and even more with 30 microM carebastine. Cell migration was inhibited by 37 and 70% in HUVECs (p < or = 0.03) and 60 and 78% in HPAECs (p < or = 0.01) in the presence of 10 and 30 microM carebastine, respectively. Carebastine (20 microM) caused a significant reduction (70-86%; p<0.01) in topological parameters of the capillary network produced in vitro by both EC lines on a basement membrane extract. Carebastine (30 and 50 microM) inhibited the VEGF-induced angiogenesis in the CAM assay in vivo two- and three-fold, respectively (p<0.001). Finally, both EC lines, on exposure to 10 and 20 microM carebastine, showed a four- to six-fold reduction (p < or = 0.01) in both VEGF- and H1 receptor-induced VEGFR-2 and Akt phosphorylation. Overall, these data provide the first evidence regarding the anti-angiogenic activity of ebastine, and suggest its potential use as an anti-angiogenic molecule, besides its antihistaminic activity for the treatment of allergic diseases in which angiogenesis takes place." @default.
• W2100057322 created "2016-06-24" @default.
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• W2100057322 date "2009-04-08" @default.
• W2100057322 modified "2023-09-27" @default.
• W2100057322 title "Anti-angiogenic activity of carebastine: a plausible mechanism affecting airway remodelling" @default.
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• W2100057322 doi "https://doi.org/10.1183/09031936.00165308" @default.
• W2100057322 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19357149" @default.
• W2100057322 hasPublicationYear "2009" @default.
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