Peroxisome Proliferator-Activated Receptor-alpha is crucial for iloprost-induced in vivo angiogenesis and VEGF upregulation

Eleonora Gaetani, Andrea Flex, Giovanni Pecorini, Roberto Pola, Federico Biscetti, Giuseppe Straface, Flavia Angelini, Egidio Stigliano, Tamar Aprahamian, Roy Smith, John Castellot

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

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.
Lingua originaleEnglish
pagine (da-a)103-108
Numero di pagine6
RivistaJournal of Vascular Research
Stato di pubblicazionePubblicato - 2009

Keywords

  • PPAR
  • VEGF
  • angiogenesis

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