Imaging of angiogenesis in inflammation and cancer: lessons for novel treatment of allergic rhinitis

Abstract

SummaryAngiogenesis is a feature of inflammatory and neoplastic disease. Imaging studies are revealing the distribution and accessibility of molecular targets at sites of angiogenesis and how abnormalities of angiogenic blood vessels can be exploited in diagnosis and treatment. Blood vessels at sites of angiogenesis have multiple abnormalities that provide targets for diagnostics and therapeutics. These abnormalities involve all components of the vessel wall, including endothelial cells, pericytes (mural cells), and the vascular basement membrane. Endothelial cells of angiogenic blood vessels in tumours may express abnormal proteins, sprout, proliferate, have a defective barrier function, and be dependent on vascular endothelial growth factor (VEGF) for survival. Endothelial cells of capillaries at sites of inflammation acquire a venule‐like phenotype, become leaky, and express adhesion molecules that support leucocyte influx. Inhibitors of VEGF signalling can stop angiogenesis, have a potent antivascular action, and reduce the abnormality of surviving vessels. Studies of VEGF inhibitors in mouse tumour models have shown robust and rapid changes in endothelial cells, pericytes, and the vascular basement membrane of angiogenic blood vessels. After treatment, endothelial fenestrations disappear, vascular sprouting is suppressed, and patency and blood flow cease in some vessels within 24 h. By 7 days, many tumour vessels regress. Surviving tumour vessels acquire more normal structural characteristics. Pericytes do not degenerate to the same extent as endothelial cells. The vascular basement membrane also persists after endothelial cells degenerate, providing a record of regressing vessels, sites for growth factor binding, and a scaffold for blood vessel regrowth after the cessation of therapy. The actions of angiogenesis inhibitors on blood vessels in tumours highlight the potential of exploiting the molecular and cellular abnormalities of angiogenic blood vessels in inflammatory conditions, including allergic rhinitis.