Chemotactic, mitogenic, and angiogenic actions of UTP on vascular endothelial cells

Endothelial cells express receptors for ATP and UTP, and both UTP and ATP e licit endothelial release of vasoactive compounds such as prostacyclin and nitric oxide; however, the distinction between purine and pyrimidine nucleo tide signaling is not known. We hypothesized that UTP plays a more importan t role in endothelial mitogenesis and chemotaxis than does ATP and that UTP is angiogenic. In cultured endothelial cells from guinea pig cardiac vascu lature (CEC), both UTP and vascular endothelial growth factor (VEGF) were s ignificant mitogenic and chemotactic factors; in contrast, ATP demonstrated no significant chemotaxis in CEC. In chick chorioallantoic membranes (CAM) , UTP and VEGF treatments produced statistically significant increases in C AM vascularity compared with controls. These findings are the first evidenc e of chemotactic or angiogenic effects of pyrimidines; they suggest a role for pyrimidine nucleotides that is distinct from those assumed by purine nu cleotides and provide for the possibility that UTP serves as an extracellul ar signal for processes such as endothelial repair and angiogenesis.