High-dose treatment with telmisartan induces monocytic peroxisome proliferator-activated receptor-gamma target genes in patients with the metabolic syndrome.

Author(s): Bahr IN, Tretter P, Kruger J, Stark RG, Schimkus J, Unger T, Kappert K, Scholze J, Parhofer KG, Kintscher U

Affiliation(s): Center for Cardiovascular Research, Institute of Pharmacology, Outpatient Clinic, Charite Campus Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany.

Publication date & source: 2011-10, Hypertension., 58(4):725-32. Epub 2011 Aug 29.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

The present study aimed to explore the anti-inflammatory effects and peroxisome proliferator-activated receptor-gamma (PPARgamma)-activating properties of the angiotensin type 1 receptor blocker telmisartan by analysis of serum interleukin 6 levels and monocytic PPARgamma target gene expression in drug-naive patients with the metabolic syndrome. This was a 14-week, randomized, double-blind, placebo-controlled 2-center study with telmisartan 80 mg/d and telmisartan 160 mg/d in 54 patients with the metabolic syndrome. In addition to clinical laboratory measurements, peripheral monocytes were extracted by negative isolation using a Dynal Monocyte kit to evaluate ligand-activated PPARgamma target gene expression (CD36 and CD163) at baseline and study end using quantitative real-time RT-PCR. In this low-risk patient population, telmisartan (80 and 160 mg) treatment did not significantly affect serum interleukin 6 levels. Expression of the PPARgamma target gene CD36 in monocytes was markedly induced by telmisartan from baseline to study end (telmisartan 80 mg: 2.3+/-1.5-fold change versus placebo [P value not significant]; telmisartan 160 mg: 3.5+/-0.9-fold change versus placebo [P<0.05]). The recently reported PPARgamma target gene CD163 was slightly induced by telmisartan (telmisartan 80 mg: 1.1+/-0.3-fold change versus placebo [P value not significant]; telmisartan 160 mg: 1.4+/-0.4-fold change versus placebo [P value not significant]), which did not reach statistical significance. This is the first clinical description of monocytic PPARgamma target gene regulation with high-dose telmisartan treatment. These data implicate that the angiotensin type 1 receptor blocker telmisartan activates PPARgamma in circulating monocytes of patients with the metabolic syndrome.