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Targeting either the extracellular domain or the cytoplasmic tail deleteriously affects the junctional strength and leads to vascular permeability. Recently, cytokine-induced phosphorylation of the vascular endothelial-cadherin cytoplasmic domain was reported to trigger cleavage of its extracellular domain, producing the soluble form of the protein \u2013 soluble vascular endothelial-cadherin. Hence, the presence of soluble vascular endothelial-cadherin or auto-antibodies to human vascular endothelial-cadherin in human serum could signalize the presence of vascular abnormalities. 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