title: Vascular hyperpermeability, angiogenesis, and stroma generation.
abstract: It has been known for more than half a century that the tumor microvasculature is hyperpermeable to plasma proteins. However, the identity of the leaky vessels and the consequences of vascular hyperpermeability have received little attention. This article places tumor vascular hyperpermeability in a broader context, relating it to (1) the low-level "basal" permeability of the normal vasculature; (2) the "acute," short-term hyperpermeability induced by vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) and other vascular permeabilizing agents; and (3) the "chronic" hyperpermeability associated with longer-term exposure to agents such as VPF/VEGF-A that accompanies many types of pathological angiogenesis. Leakage of plasma protein-rich fluids is important because it activates the clotting system, depositing an extravascular fibrin gel provisional matrix that serves as the first step in stroma generation.
authors.affiliation: Center for Vascular Biology Research and the Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Nagy
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dvorak
authors.forename: Harold F
authors.initials: HF
authors.lastname: Dvorak
mesh_terms: D001681:Biological Assay / Q000379:methods; D001779:Blood Coagulation Factors / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000098:blood supply* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology; D012709:Serum Albumin / Q000502:physiology; D017154:Stromal Cells / Q000473:pathology* / Q000502:physiology; D009626:Terminology as Topic; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D014699:Venules / Q000473:pathology / Q000503:physiopathology
chemical_list: D001779:Blood Coagulation Factors; D005353:Fibronectins; D007136:Immunoglobulins; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A