Vascular endothelial growth factor and microvascular permeability

Vascular Endothelial Growth Factors (VEGFs) are endogenously produced vascular cytokines which result in angiogenesis, vasodilatation, and increased microvascular permeability in vivo. They are endothelial specific and result in mitosis, migration, stress fiber formation and increased permeability of endothelial cells in culture. They have been critically implicated in a host of pathological conditions including solid tumor growth and diabetes, and been proposed as a therapy for coronary and peripheral ischemic disease. However, the potent permeability-enhancing properties of VEGFs are very poorly understood. The pharmacology, signal transduction pathways, intracellular signaling mechanisms, and ultrastructural changes which result in increased permeability are still not clear. This review discusses the available evidence for how VEGFs increase permeability in vivo, and some of the pitfalls in interpreting experiments which do not take into account the vasoactive properties of VEGFs. It also discusses the clinical implications of the permeability enhancing effect of VEGFs, and the relevance of these studies to development of new therapies.