Peroxisome Proliferator-Activated Receptor (PPAR) High-Dose Treatment With Telmisartan Induces Monocytic Peroxisome Proliferator-Activated Receptor- Target Genes in Patients With the Metabolic Syndrome

The present study aimed to explore the anti-inflammatory effects and peroxisome proliferator-activated receptor(PPAR )–activating properties of the angiotensin type 1 receptor blocker telmisartan by analysis of serum interleukin 6 levels and monocytic PPAR target gene expression in drug-naı̈ve 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 PPAR 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 PPAR 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 PPAR 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 PPAR target gene regulation with high-dose telmisartan treatment. These data implicate that the angiotensin type 1 receptor blocker telmisartan activates PPAR in circulating monocytes of patients with the metabolic syndrome. (Hypertension. 2011;58:725-732.) ● Online Data Supplement