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Tesi etd-10072008-130335


Thesis type
Tesi di dottorato di ricerca
Author
DEL FIORENTINO, ALESSANDRA
URN
etd-10072008-130335
Title
Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells
Settore scientifico disciplinare
BIO/10
Corso di studi
FISIOPATOLOGIA E CLINICA DELL'APPARATO CARDIOVASCOLARE E RESPIRATORIO
Commissione
Relatore Prof. Pedrinelli, Roberto
Relatore Dott.ssa Cianchetti, Silvana
Parole chiave
  • endothelial cells
  • angiotensin receptor blockers
  • adhesion molecules
  • oxidative damage
  • telmisartan
Data inizio appello
06/12/2008;
Consultabilità
completa
Riassunto analitico
Purpose: To study whether telmisartan, an angiotensin II (AII) receptor blocker (ARB), modulates endothelial inflammation and oxidative cell damage induced by AII-independent stimuli in cultured human umbilical vein endothelial cell (HUVEC)s.<br>Methods: Endothelial inflammation, as reflected by increased VCAM-1 and ICAM-1 expression (ELISA), was induced by TNF-alpha, an inflammatory cytokine, and cell damage (COMET and MTT assay) by hydrogen peroxide, a reactive oxygen species. Losartan, another ARB, its active metabolites (EXP-3174, EXP-3179), dexamethasone, a synthetic steroid, and pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, were the controls. The contribution of PPAR-gamma agonism was assessed through synthetic PPAR-gamma agonists and antagonists and the antagonism for AII-type 1 receptor-mediated stimuli by evaluating the interference against cell death induced by AII (MTT assay), a pro-apoptotic peptide that induces oxidative stress. The in vitro scavenging properties for oxyradicals were quantified by the TOSC assay.<br>Results: Telmisartan and PDTC reduced TNF-alpha-stimulated VCAM-1 in a concentration-dependent manner while losartan, EXP-3174, EXP-3179 and dexamethasone were ineffective. All compounds did not modify ICAM-1 expression. PPAR-gamma agonists or antagonists did not interfere with the effect of telmisartan. Both ARBs antagonized AII-induced cell death but only telmisartan reduced hydrogen peroxide-induced cell damage. Telmisartan scavenged selectively hydroxyl radicals without affecting peroxyl radicals and peroxynitrite.<br>Conclusions: Telmisartan modulates pleiotropically TNF-alpha induced VCAM-1 expression and oxidative damage in vascular endothelium, possibly by acting as a hydroxyl radical scavenger. Those anti-inflammatory and antioxidant properties may contribute to the therapeutic effect, although the applicability of these data to the clinical situations has to be verified.
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