PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB-mediated COX-2 expression in the human endothelium (Articolo in rivista)

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  • PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB-mediated COX-2 expression in the human endothelium (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Scoditti E.; Massaro M.; Carluccio M. A.; Distante A.; Storelli C.; De Caterina R. (2010)
    PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB-mediated COX-2 expression in the human endothelium
    in Cardiovascular research
    (literal)
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  • Scoditti E.; Massaro M.; Carluccio M. A.; Distante A.; Storelli C.; De Caterina R. (literal)
Pagina inizio
  • 302 (literal)
Pagina fine
  • 310 (literal)
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  • 86 (literal)
Rivista
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  • In: Cardiovascular Research, vol. 86 (2) pp. 302 - 310. Oxford Journal, 2010. (literal)
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  • 9 (literal)
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  • PubMe (literal)
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  • C.N.R. Institute of Clinical Physiology, Lecce, Italy; Department of Biological and Environmental Sciences and Technologies (Disteba), University of Salento, Lecce, Italy; Cardio-Thoracic Department, University of Pisa, Pisa, Italy; and Institute of Cardiology and Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy (literal)
Titolo
  • PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB-mediated COX-2 expression in the human endothelium (literal)
Abstract
  • AIMS: The activation of peroxisome proliferator-activated receptor (PPAR)gamma is known to inhibit angiogenesis. As a potential mechanism for this, we aimed at examining the effects of PPARgamma agonists on the pro-angiogenic enzyme cyclooxygenase (COX)-2 in human endothelium. METHODS AND RESULTS: Cultured endothelial cells were pre-incubated with the PPARgamma agonists rosiglitazone (RSG) or GW1929 before stimulation with vascular endothelial growth factor (VEGF) or phorbol myristate acetate (PMA). RSG and GW1929 attenuated VEGF- and PMA-stimulated COX-2 activity, as well as protein and mRNA expression. This effect was abolished by the PPARgamma antagonists bisphenol A diglycidyl ether and GW9662 as well as by PPARgamma small-interfering RNAs (siRNAs). Transient transfection experiments revealed that the induction of COX-2 promoter was significantly inhibited by RSG through an interference with the cAMP response element (CRE) site. COX-2 downregulation after siRNA targeting CRE-binding protein (CREB) confirmed the role of CREB in mediating COX-2 transcription. Correspondingly, PPARgamma agonists attenuated CREB activation. As both protein kinase C (PKC)alpha and beta are involved in VEGF-induced COX-2 expression and CREB activation, we investigated which isoform(s) of PKC was affected by RSG. RSG only reduced VEGF- and PMA-stimulated PKCalpha membrane translocation. CONCLUSION: VEGF induces CREB-mediated COX-2 expression through a PKCalpha-dependent pathway in human endothelium. The anti-angiogenic effect of PPARgamma agonists is due, at least in part, to an interference with the VEGF-stimulated PKCalpha-mediated activation of CREB and the related expression of COX-2 (literal)
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