Vascular hyperpermeability, angiogenesis, and stroma generation

JA Nagy, AM Dvorak… - Cold Spring …, 2012 - perspectivesinmedicine.cshlp.org
JA Nagy, AM Dvorak, HF Dvorak
Cold Spring Harbor perspectives in medicine, 2012perspectivesinmedicine.cshlp.org
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) …
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.
perspectivesinmedicine.cshlp.org