title: Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Dipartimento Cardio Toracico e Vascolare, Università di Pisa, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Cianchetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Fiorentino
authors.forename: Renato
authors.initials: R
authors.lastname: Colognato
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stefano
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Franzoni
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedrinelli
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D047495:PPAR gamma / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014657:Vasculitis / Q000188:drug therapy*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D016877:Oxidants; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D000077333:Telmisartan