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 (PAF), a phospholipid mediator of inflammation that possesses angiogenic properties. The synthesis of PAF by HUVEC stimulated with Tat was dose and time dependent. Moreover, in vitro experiments were performed to evaluate whether 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 2170, 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 results suggest that the synthesis of PAF by endothelial cells mediates, at least in part, the angiogenic activity of Tat by promoting the endothelial cell migration.
Del Sorbo
L
L
Dipartimento di Medicina Interna, Università di Torino, Torino, Italy.
Arese
M
M
Giraudo
E
E
Tizzani
M
M
Biancone
L
L
Bussolino
F
F
Camussi
G
G
D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D014230:Triazoles / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D043925:Angiogenesis Inducing Agents; D001381:Azepines; D015696:Gene Products, tat; D010972:Platelet Activating Factor; D014230:Triazoles; D054322:tat Gene Products, Human Immunodeficiency Virus; C063964:bepafant