Article date: January 2003
By: Maria Grazia Cattaneo, Sandra Pola, Valeria Dehò, Anna Maria Sanguini, Lucia Maria Vicentini in Volume 138, Issue 2, pages 377-385
Prostaglandin E1 (PGE1, alprostadil) is used as a vasodilator for the treatment of peripheral vascular diseases.
Previous reports suggested a pro‐angiogenic effect for PGE1.
We studied the in vitro and in vivo effect of PGE1, complexed with α‐cyclodextrin, on the angiogenic process. Contrary to what was expected, we found that, in human umbilical vein endothelial cells (HUVECs), PGE1 inhibited proliferation, migration and capillary‐like structure formation in Matrigel.
By RT–PCR studies, the expression of the EP2 and EP3 subtypes of the PG receptor was detected in HUVECs.
PGE1 alone stimulated adenylate cyclase activity at micromolar concentrations, while at nanomolar concentrations potentiated the forskolin‐induced cAMP accumulation.
8‐Bromoadenosine‐3′:5′‐cyclic monophosphate (Br‐cAMP) mimicked the inhibitory effect of PGE1 on endothelial cell growth, motility and tube formation.
Sulprostone, an agonist at the EP3 subtype of PG receptors, mimicked the in vitro anti‐angiogenic effects of PGE1, while butaprost, an EP2 receptor agonist, had no effect.
Finally, in the plug assay model of angiogenesis in mice, PGE1 showed a strong inhibitory effect on Matrigel neovascularization.
Thus, PGE1 possesses strong anti‐angiogenic activity in vitro and in vivo.
Prostaglandin E1 (PGE1, alprostadil) is used as a vasodilator for the treatment of peripheral vascular diseases.
Previous reports suggested a pro‐angiogenic effect for PGE1.
We studied the in vitro and in vivo effect of PGE1, complexed with α‐cyclodextrin, on the angiogenic process. Contrary to what was expected, we found that, in human umbilical vein endothelial cells (HUVECs), PGE1 inhibited proliferation, migration and capillary‐like structure formation in Matrigel.
By RT–PCR studies, the expression of the EP2 and EP3 subtypes of the PG receptor was detected in HUVECs.
PGE1 alone stimulated adenylate cyclase activity at micromolar concentrations, while at nanomolar concentrations potentiated the forskolin‐induced cAMP accumulation.
8‐Bromoadenosine‐3′:5′‐cyclic monophosphate (Br‐cAMP) mimicked the inhibitory effect of PGE1 on endothelial cell growth, motility and tube formation.
Sulprostone, an agonist at the EP3 subtype of PG receptors, mimicked the in vitro anti‐angiogenic effects of PGE1, while butaprost, an EP2 receptor agonist, had no effect.
Finally, in the plug assay model of angiogenesis in mice, PGE1 showed a strong inhibitory effect on Matrigel neovascularization.
Thus, PGE1 possesses strong anti‐angiogenic activity in vitro and in vivo.
British Journal of Pharmacology (2003) 138, 377–385. doi:10.1038/sj.bjp.0705051
DOI: 10.1038/sj.bjp.0705051
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