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REGULATION OF VASCULOGENESIS AND ANGIOGENESIS
Citation:
Abbott, B D. REGULATION OF VASCULOGENESIS AND ANGIOGENESIS. Presented at Teratology Society Meeting, Palm Beach, FL, June 24 - 29, 2000.
Description:
Regulation of vasculogenesis and angiogenesis.
B.D. Abbott
Reproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA
Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and ligands. The members of this pathway include multiple isoforms of vascular endothelial cell growth factor (VEGF). The receptors that bind VEGF are differentially expressed in the placenta and embryo and each receptor (VEGF-R1, VEGF-R2) regulates specific events in vasculogenesis. Tie2, neuropillin-1, Ang1 and Ang2 (angiopoietin) are also important in angiogenesis or remodeling of the vasculature. Knock-out of these genes produces phenotypes and lethality which depend on and confirm the functionality of each member of the pathway. Normal reproductive function in the adult depends on steroid hormonal regulation of the VEGF pathway and disruption (possibly through endocrine disrupting compounds) would be expected to impact ovarian, uterine, and testicular function, as well as having negative impact on pregnancy maintenance, conceptus implantation, vascularization of placenta, yolk sac and embryo. The VEGF gene pathways are also regulated by hypoxia through interaction of HIF1-alpha and ARNT. Knockout of either protein is lethal to the conceptus early in gestation. The mechanisms through which ARNT knockout affects placental vascularization includes effects on VEGF binding and expression of a VEGF receptor in the placental labyrinth. This presentation will provide an overview of the complex, interactive cascade of receptors and ligands which control vasculogenesis and angiogenesis in the conceptus and adult. Disclaimer: This abstract does not necessarily reflect EPA policy.