We have previously demonstrated that iloprost, a stable prostacyclin (PGI2) analogue, induces angiogenesis in vivo, through a vascular endothelial growth factor (VEGF)-dependent mechanism. In this study, we demonstrate that iloprost-induced angiogenesis and VEGF upregulation are modulated by peroxisome proliferator-activated receptor-α (PPARα), a ligand-inducible transcription factor that belongs to the nuclear hormone receptor superfamily and plays multiple biological activities in the vascular system. We show that iloprost is unable to induce angiogenesis in mice lacking the PPARα gene (PPARα-/- mice). Likewise, iloprost-induced VEGF upregulation is absent in PPARα-/- mice. In contrast, iloprost induces a robust angiogenic response in wild-type mice, along with local upregulation of VEGF. Importantly, mice lacking the PPARα gene exhibit a normal angiogenic response to VEGF, indicating that the absence of PPARα does not result in a general impairment of angiogenesis, but specifically affects the ability of iloprost to induce angiogenesis. Our data demonstrate unexpected functional relationships between the PGI2 system and the PPAR signaling pathway and shed new light on the molecular mechanisms involved in iloprost-induced angiogenesis. Copyright © 2008 S. Karger AG.
Biscetti, F., Gaetani, E., Flex, A., Straface, G., Pecorini, G., Angelini, F., Stigliano, E., Aprahamian, T., Smith, R. C., Castellot, J. J., Pola, R., Peroxisome proliferator-activated receptor alpha is crucial for iloprost-induced in vivo angiogenesis and vascular endothelial growth factor upregulation, <<JOURNAL OF VASCULAR RESEARCH>>, 2009; 46 (2): 103-108. [doi:10.1159/000143793] [https://hdl.handle.net/10807/305656]
Peroxisome proliferator-activated receptor alpha is crucial for iloprost-induced in vivo angiogenesis and vascular endothelial growth factor upregulation
Biscetti, Federico;Gaetani, Eleonora;Flex, Andrea;Straface, Gianluca;Pecorini, Giovanni;Stigliano, Egidio;Pola, Roberto
2009
Abstract
We have previously demonstrated that iloprost, a stable prostacyclin (PGI2) analogue, induces angiogenesis in vivo, through a vascular endothelial growth factor (VEGF)-dependent mechanism. In this study, we demonstrate that iloprost-induced angiogenesis and VEGF upregulation are modulated by peroxisome proliferator-activated receptor-α (PPARα), a ligand-inducible transcription factor that belongs to the nuclear hormone receptor superfamily and plays multiple biological activities in the vascular system. We show that iloprost is unable to induce angiogenesis in mice lacking the PPARα gene (PPARα-/- mice). Likewise, iloprost-induced VEGF upregulation is absent in PPARα-/- mice. In contrast, iloprost induces a robust angiogenic response in wild-type mice, along with local upregulation of VEGF. Importantly, mice lacking the PPARα gene exhibit a normal angiogenic response to VEGF, indicating that the absence of PPARα does not result in a general impairment of angiogenesis, but specifically affects the ability of iloprost to induce angiogenesis. Our data demonstrate unexpected functional relationships between the PGI2 system and the PPAR signaling pathway and shed new light on the molecular mechanisms involved in iloprost-induced angiogenesis. Copyright © 2008 S. Karger AG.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.