Vascular protection - A novel nonangiogenic cardiovascular role for vascular endothelial growth factor

There is widespread interest in the use of the angiogenic cytokine, vascula r endothelial growth factor (VEGF), for the treatment of cardiovascular dis ease. The main paradigm for VEGF cardiovascular therapy is the stimulation of "therapeutic angiogenesis" in ischemic myocardial and peripheral vascula r limb disease. In this review, approaches to VEGF therapy based on the the rapeutic angiogenesis model are critically assessed, and the alternative me chanism of vascular protection is advanced. Vascular protection is defined as the VEGF-induced enhancement of endothelial functions that mediate the i nhibition of vascular smooth muscle cell proliferation, enhanced endothelia l cell survival, suppression of thrombosis, and anti-inflammatory effects. VEGF-induced synthesis of NO and prostacyclin are both likely to be key med iators of VEGF-dependent vascular protection. Investigation into vascular p rotection should help us to gain insight into the underlying mechanisms of the cardiovascular actions of VEGF and should prove valuable in the develop ment of novel therapeutic approaches based on local VEGF gene delivery.