EG-VEGF and Bv8: a novel family of tissue-restricted angiogenic factors

Abstract

A novel family of angiogenic mitogens have been recently characterized. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), and the mammalian homologue of Bombina variegata peptide 8 (Bv8), are two highly related endothelial cell mitogens and chemotactic factors with restricted expression profiles and selective endothelial cell activity. These peptides share two cognate G-protein coupled receptors. The expression of human EG-VEGF occurs predominantly in steroidogenic glands. Consistent with such an expression pattern, the human EG-VEGF gene promoter has a potential binding site for steroidogenic factor (SF)-1, a pivotal element for steroidogenic-specific transcription. In the human ovary, the expression of EG-VEGF is temporally and spatially complementary to the expression of VEGF-A, both in the follicular and in the luteal phase, suggesting complementary and coordinated roles of these molecules in ovarian angiogenesis. Also, EG-VEGF expression correlates with vascularity in the polycystic ovary syndrome, a leading cause of infertility. Bv8 expression is mainly restricted to the testis. The identification of these tissue-selective angiogenic factors raises the possibility that other secreted molecules with selectivity for the endothelium of other organs exist.