Role of vascular endothelial growth factor in diabetic vascular complications

Background. Much of the morbidity and mortality associated with diabetes me llitus predominantly reflects its deleterious effects on microcirculation a nd macrocirculation. During the past few years, rapid advancement has been made in our understanding of the mechanisms and molecules involved in the p athogonesis of diabetic microvasculopathy. This is particularly true with r egard to retinal vascular disease and the role of the angiogenesis- and vas opermeability-inducing molecule, vascular endothelial growth factor (VEGF). Methods. Biochemical studies in many relevant cell types have been performe d. Effects of VEGF action and inhibition have been evaluated in animals. In terventions that block the biochemical pathways initiated by VEGF have been tested both in culture and in animals. Human clinical trials have begun. Results. VEGF induces vascular endothelial cell proliferation, migration an d vasopermeability in many cells and tissues. In vivo, VEGF has been identi fied as a primary initiator of proliferative diabetic retinopathy, and as a potential mediator of nonproliferative retinopathy. In addition, VEGF has been implicated in the development of neuropathy and nephropathy in the pat ient with diabetes. In patients with diabetes and coronary artery or periph eral vascular disease, VEGF may induce development of cardiac and limb vasc ular collateralization, respectively. Many biochemical processes mediating these actions have now been elucidated. Conclusions. VEGF appears to play a central role in mediating diabetic vasc ulopathy in many organs. Improved understanding of the molecular mechanisms underlying these processes has permitted development of novel therapeutic interventions, several of which are now in human clinical trials. These sci entific advances and various implications for the future care of vasculopat hy associated with diabetes will be discussed.