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result sql = Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation independently of the peroxisome proliferator-activated receptor-gamma.
Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation independently of the peroxisome proliferator-activated receptor-gamma.
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result sql = Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used to treat patients with hypertension. Telmisartan, in addition to its effect on AT1R, is thought to activate the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial PPAR gamma agonist. This study was conducted to examine whether telmisartan might suppress cytokine-induced inflammatory signaling in vascular endothelial cells, thereby attenuating cellular inflammation possibly by PPAR gamma activation. Telmisartan caused a dose-dependent suppression of the tumor necrosis factor-alpha (TNFalpha)-induced activation of nuclear factor (NF)-kappaB in vascular endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not influence the inhibitory effect of telmisartan on NF-kappaB activation. The thiazolidinediones neither influenced TNFalpha-induced NF-kappaB activation nor influenced the inhibitory effect of telmisartan in this process. Telmisartan dose dependently diminished the TNFalpha-induced gene expression of VCAM-1, and GW9662 did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.

Publication: Hypertens. Res. 2009 Sep ;32(9)::765-9. :doi: 10.1038/hr.2009.95.
Publication Date: 2009 Sep
Study Author(s): Nakano, Ayuko;Hattori, Yoshiyuki;Aoki, Chie;Jojima, Teruo;Kasai, Kikuo;
Institution: Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Shortcut link to this study:
Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used to treat patients with hypertension. Telmisartan, in addition to its effect on AT1R, is thought to activate the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial PPAR gamma agonist. This study was conducted to examine whether telmisartan might suppress cytokine-induced inflammatory signaling in vascular endothelial cells, thereby attenuating cellular inflammation possibly by PPAR gamma activation. Telmisartan caused a dose-dependent suppression of the tumor necrosis factor-alpha (TNFalpha)-induced activation of nuclear factor (NF)-kappaB in vascular endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not influence the inhibitory effect of telmisartan on NF-kappaB activation. The thiazolidinediones neither influenced TNFalpha-induced NF-kappaB activation nor influenced the inhibitory effect of telmisartan in this process. Telmisartan dose dependently diminished the TNFalpha-induced gene expression of VCAM-1, and GW9662 did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.
PMID: 19590508

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