Sympathetic Control of VEGF Angiogenic Signaling

Abstract

See related article, pages 682–691 It is now accepted that vascular endothelial growth factor (VEGF), a dimeric 46-kDa heparin-binding glycoprotein, is one of the most important vasculogenic and angiogenic factors reported to date. VEGF acts as a potent and specific mitogen for vascular endothelial cells in vitro and possesses a signal sequence which allows it to be secreted.1 Furthermore, numerous studies in vivo have shown that expression of VEGF and its receptors is upregulated during angiogenesis under physiological and pathological processes, such as development of the embryo,2–4 estrous cycle,5 tumor growth,6,7 and wound healing.8 Thus, VEGF plays an important role in the formation of new vessels from existing ones and the microvascular remodeling which involves structural alterations—usually enlargement—of arterioles, capillaries, or venules, in inflammatory or neoplastic diseases. Different mechanisms appear to participate in the regulation of VEGF mRNA expression. It is well known that low oxygen tension is a strong inducer of VEGF mRNA expression in a variety of cells.6,9 Besides hypoxia-sensitive elements, the VEGF promoter region contains potential binding sites for the transcription factors AP-1, AP-2, and SP-1.10 Consistent with this fact, cAMP analogues and phorbol esters have been shown to …