Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells

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. 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 All-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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.