The Role of VEGF in Controlling Vascular Permeability

Blood vessels in different organs have vastly different morphologies and functions. One important aspect of vessel heterogeneity is its exchange with the surrounding tissue. While vessels in the CNS are highly restricted in their exchange, vessels in peripheral organs may be quite permeable and allow solvent and small molecules to pass across the vessel wall. A more extensive permeability, or leakage, can be induced in an acute, transient manner by specific factors, with the purpose to deliver blood constituents to the interstitial space. The interstitial fluid is drained by the lymphatic vasculature and eventually delivered back to the blood circulation via the subclavian veins. Larger volumes of accumulated interstitial fluid, edema, are a sign of extensive leakage and/or poor uptake of fluid by the lymphatics. Through the continuous blood and lymphatic circulation, the maintenance of tissue homeostasis is ensured through the delivery of oxygen and nutrients to the tissues. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and leaky vessels with poor blood flow and tissue swelling potentially exacerbated by poorly functioning lymphatics. Elevated interstitial pressure, hypoxia, and a chaotic tissue microenvironment promote the disease. This review is focused on the role of vascular endothelial growth factors (VEGFs) and their receptors in the control of vessel integrity.