The Antidiabetic Peroxisome Proliferator Activated Receptor (PPAR)gamma agonist rosiglitazone inhibits COX-2-mediated angiogenesis by suppressing both PKCalpha and CREB activation (Abstract in rivista)

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  • The Antidiabetic Peroxisome Proliferator Activated Receptor (PPAR)gamma agonist rosiglitazone inhibits COX-2-mediated angiogenesis by suppressing both PKCalpha and CREB activation (Abstract in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Scoditti E.; Massaro M.; Carluccio M. A.; Storelli C.; Distante A.; De Caterina R. (2007)
    The Antidiabetic Peroxisome Proliferator Activated Receptor (PPAR)gamma agonist rosiglitazone inhibits COX-2-mediated angiogenesis by suppressing both PKCalpha and CREB activation
    in European Heart Journal, 2007
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Scoditti E.; Massaro M.; Carluccio M. A.; Storelli C.; Distante A.; De Caterina R. (literal)
Convegno
  • European Heart Journal (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • In: European Heart Journal, vol. 28 pp. 611 - 611. Oxford University Press, 2007. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Introduction: The activation of PPARgamma by the antidiabetic drug RSG is known to inhibit angiogenesis associated with diabetic vasculopathy, but underlying mechanisms are still unknown. The transcription factor cAMP-response element-binding protein (CREB) plays a key role in promoting angiogenesis in part regulating the expression of the pro-angiogenic enzyme COX-2. Methods: We investigated the effects of RSG on COX-2 expression and CREB activation in human umbilical vein endothelial cells challenged with the pro-angiogenic agents VEGF and PMA. Results: 10 m mol/L RSG inhibited COX-2 expression and activity (by 40%, at Western blot and immunoassays for 6-keto-PGF1alpha) as induced by VEGF and PMA. This effect was mostly due to the inhibition of CREB activation since RSG significantly reduced CREB phosphorylation (by 30% at Western analysis). Since Protein Kinase (PK)C is involved in VEGF-induced angiogenesis and COX-2 expression, we investigated which isoform(s) of PKC was affected by RSG. We observed that while the inhibition of both conventional ± and b PKC isoforms suppressed VEGF- and PMA- stimulated CREB activation and COX-2 expression (by 70% and 80%, respectively, Western blot), RGS reduced only the VEGF- and PMA-stimulated PKCalpha membrane translocation (by 30%, Western blot) leaving PKCbeta activation unaffected. Conclusions: Our findings indicate that VEGF induces CREB-mediated COX-2 expression through a PKC-dependent pathway in human endothelium, and that the anti-angiogenic effect of RSG is due to its interference with the PKCalpha-mediated activation of CREB and related expression of COX-2. (literal)
Titolo
  • The Antidiabetic Peroxisome Proliferator Activated Receptor (PPAR)gamma agonist rosiglitazone inhibits COX-2-mediated angiogenesis by suppressing both PKCalpha and CREB activation (literal)
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