title: Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin.
abstract: Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore, inhibitors of endothelial cell function could reduce inflammation. In this study, we evaluated the effects of the angiogenesis inhibitor vasostatin on inflammations induced by contact hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed significantly reduced edema formation, resulting from lower plasma leakage and inhibition of inflammation-associated vascular remodeling. Intravital microscopy studies of inflamed ears showed a decrease in the fraction of rolling leukocytes in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears revealed fewer leukocytes adherent to the vessel wall. The inflammatory infiltrate from vasostatin-treated mice was characterized by fewer CD8+ T cells, neutrophils, and macrophages compared to the saline-treated animals. In a modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A-induced permeability, and inflamed ear tissues from vasostatin-treated mice expressed significantly reduced levels of the vascular destabilizer angiopoietin-2. These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation.
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Huegel
authors.forename: Paula
authors.initials: P
authors.lastname: Velasco
authors.forename: Maria
authors.initials: M
authors.lastname: De la Luz Sierra
authors.forename: Enno
authors.initials: E
authors.lastname: Christophers
authors.forename: Jens M
authors.initials: JM
authors.lastname: Schröder
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lange-Asschenfeldt
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D037282:Calreticulin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D037282:Calreticulin; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C121986:vasostatin