title: High-dose treatment with telmisartan induces monocytic peroxisome proliferator-activated receptor-γ target genes in patients with the metabolic syndrome.
abstract: The present study aimed to explore the anti-inflammatory effects and peroxisome proliferator-activated receptor-γ (PPARγ)-activating properties of the angiotensin type 1 receptor blocker telmisartan by analysis of serum interleukin 6 levels and monocytic PPARγ target gene expression in drug-naïve 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 PPARγ 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 PPARγ 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 PPARγ 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 PPARγ target gene regulation with high-dose telmisartan treatment. These data implicate that the angiotensin type 1 receptor blocker telmisartan activates PPARγ in circulating monocytes of patients with the metabolic syndrome.
authors.affiliation: Center for Cardiovascular Research, Institute of Pharmacology, Outpatient Clinic, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ilse-Nirmala
authors.initials: IN
authors.lastname: Bähr
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tretter
authors.forename: Janine
authors.initials: J
authors.lastname: Krüger
authors.forename: Renee G
authors.initials: RG
authors.lastname: Stark
authors.forename: Julia
authors.initials: J
authors.lastname: Schimkus
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scholze
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
mesh_terms: D000328:Adult; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000494:pharmacology; D000098902:CD163 Antigen
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001562:Benzimidazoles; D001565:Benzoates; D000098902:CD163 Antigen; D018955:CD36 Antigens; D015850:Interleukin-6; D047495:PPAR gamma; D011956:Receptors, Cell Surface; D045162:Thiazolidinediones; D000077333:Telmisartan; D000077205:Pioglitazone