Tat-induced platelet-activating factor synthesis contributes to the angiogenic effect of HIV-1 Tat

This study shows that human umbilical cord vein-derived endothelial cells ( HUVEC) stimulated with HIV-1 Tat synthesized platelet-activating factor (PA F), a phospholipid mediator of inflammation that possesses angiogenic prope rties. The synthesis of PAF by HUVEC stimulated with Tat was dose and time dependent. Moreover, in vitro experiments were performed to evaluate whethe r migration of HUVEC induced by Tat was dependent on the synthesis of PAF. It was found that the cell motility induced by Tat was inhibited by WEB 217 0, a specific PAF receptor antagonist. In vivo, the neoangiogenesis induced by Tat was also inhibited by WEB 2170 in a murine model, in which matrigel subcutaneously injected was used as substratum for angiogenesis. These res ults suggest that the synthesis of PAF by endothelial cells mediates, at le ast in part, the angiogenic activity of Tat by promoting the endothelial ce ll migration.