Flt-1 expression influences apoptotic susceptibility of vascular smooth muscle cells through NF-kappaB / IAP-1 pathway (Articolo in rivista)

Type
Label
  • Flt-1 expression influences apoptotic susceptibility of vascular smooth muscle cells through NF-kappaB / IAP-1 pathway (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1093/cvr/cvp288 (literal)
Alternative label
  • Orlandi A, Ferlosio A, Arcuri G, Scioli MG, De Falco S, Spagnoli LG. (2010)
    Flt-1 expression influences apoptotic susceptibility of vascular smooth muscle cells through NF-kappaB / IAP-1 pathway
    in Cardiovascular research; Oxford University Press, Oxford (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Orlandi A, Ferlosio A, Arcuri G, Scioli MG, De Falco S, Spagnoli LG. (literal)
Pagina inizio
  • 214 (literal)
Pagina fine
  • 223 (literal)
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  • http://cardiovascres.oxfordjournals.org/content/85/1/214.long (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 85 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • PMID: 19720604 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 1 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Univ Roma Tor Vergata, Dept Biopathol & Image Diagnost, I-00133 Rome, Italy 2. CNR, Inst Genet & Biophys, I-80131 Naples, Italy (literal)
Titolo
  • Flt-1 expression influences apoptotic susceptibility of vascular smooth muscle cells through NF-kappaB / IAP-1 pathway (literal)
Abstract
  • Aims Flt-1 is an fms-like tyrosine kinase receptor which binds to vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Ligand activation and blocking of flt-1 influence several vascular smooth muscle cell (SMC) functions, including apoptotic susceptibility. However, downstream signal transduction pathways by which flt-1 regulates SMC apoptosis have still to be investigated. Methods and results Flt-1 expression and apoptosis in Wistar rat aortic intimal cells 15 days after ballooning were studied by immunohistochemistry, cytometry, cell sorting, western blotting, and PCR. Anti-flt1 blocking antibody effects were compared with those of anti-PlGF and anti-VEGF antibodies. Rat aortic intimal cells 15 days after injury exhibited increased flt-1 protein and mRNA and lower smooth muscle markers compared with normal media SMCs. Immunoreactivity for flt-1 protein was also observed in apoptotic intimal cells. Anti-flt-1 (EC(50) = 16.5 ng/mL) and anti-PlGF (EC(50) = 20.5 ng/mL) antibodies added to intimal cultures reduced serum-deprived apoptosis but not serum-and PDGF-BB-induced proliferation; the anti-VEGF antibody was ineffective. Sorted flt-1(+) cells were more clonogenic than flt-1 and whole intimal SMC populations. Increased nuclear factor-kappaB (NF-kappa B) and inhibitor of apoptosis protein-1 (IAP-1) and reduced bax levels associated with the anti-flt-1-induced increase of intimal SMC survival; the latter was prevented by NF-kappa B activity inhibitor and IAP-1 interfering RNA (RNAi). Blocking of NF-kappa B activity reduced IAP-1 expression and prevented IAP-1 RNAi effects. Increased flt-1 immunoreaction was also documented in human atheromatous lesions. Conclusion Our results show that anti-flt-1 blocking reduces apoptosis through NF-kappa B and the downstream IAP-1 pathway. The close link between flt-1, PlGF, and apoptotic susceptibility of intimal SMCs suggests new potential strategies aimed at influencing post-injury arterial remodelling. (literal)
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