![]() Angiopoietin-2 abrogated the MMD serum-induced morphology change and VE-cadherin localization (n = 3 independent experiments each including at least five different patients’ sera of each group). (c) Treated cEND cells were stained for VE-cadherin (green), Ang-2 (red), and DAPI (blue) in order to visualize cell nuclei. (b) Gene expression of claudin-5, occludin and VE-cadherin in response to human serum and angiopoietin-2 blockade was analyzed by real-time qPCR. (a) Effects of recombinant Ang-1 on secretion of Ang-2 analyzed by ELISA assay. CEND cells were pre-stimulated with recombinant angiopoietin-1 (10 or 20 ng/mL) in the presence of His1 Tag cross-linking antibody (5 µg/mL) or left untreated for 2 h prior to exposition to 2.5% patients’ serum for 24 or 48 h, as indicated. Moyamoya angiogenesis cell culture cerebrovascular disease stroke.ĮC barrier stability upon blocking angiopoietin-2 in MMD serum-incubated cENDs. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. ![]() ![]() The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes.
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