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-α, 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-γ agonism was assessed through synthetic PPAR-γ 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-α-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-γ 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-α 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. © 2007 Elsevier Ireland Ltd. All rights reserved.
CITATION STYLE
Cianchetti, S., Del Fiorentino, A., Colognato, R., Di Stefano, R., Franzoni, F., & Pedrinelli, R. (2008). Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis, 198(1), 22–28. https://doi.org/10.1016/j.atherosclerosis.2007.09.013
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