Center for Cardiovascular Research, Institute of Pharmacology, Outpatient Clinic, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Hypertension. 2011 Oct;58(4):725-32. doi: 10.1161/HYPERTENSIONAHA.111.173542. Epub 2011 Aug 29.
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.
本研究旨在通过分析血清白细胞介素 6 水平和单核细胞过氧化物酶体增殖物激活受体-γ（PPARγ）靶基因表达，探讨血管紧张素 1 型受体阻滞剂替米沙坦对代谢综合征患者的抗炎作用和 PPARγ 激活特性。这是一项为期 14 周、随机、双盲、安慰剂对照的 2 中心研究，共纳入 54 例代谢综合征患者，分别给予替米沙坦 80mg/d 和 160mg/d。除了临床实验室检测外，还通过 Dynal Monocyte 试剂盒使用阴性分离法提取外周血单核细胞，以评估配体激活的 PPARγ 靶基因（CD36 和 CD163）在基线和研究结束时的表达情况，采用实时定量 RT-PCR 法。在这一低风险患者人群中，替米沙坦（80 和 160mg）治疗并未显著影响血清白细胞介素 6 水平。替米沙坦治疗可显著诱导单核细胞中 PPARγ 靶基因 CD36 的表达，从基线至研究结束时（替米沙坦 80mg：与安慰剂相比变化倍数为 2.3±1.5 倍[P 值无统计学意义]；替米沙坦 160mg：与安慰剂相比变化倍数为 3.5±0.9 倍[P<0.05]）。最近报道的 PPARγ 靶基因 CD163 也被替米沙坦轻度诱导（替米沙坦 80mg：与安慰剂相比变化倍数为 1.1±0.3 倍[P 值无统计学意义]；替米沙坦 160mg：与安慰剂相比变化倍数为 1.4±0.4 倍[P 值无统计学意义]），但未达到统计学显著性。这是首次临床描述高剂量替米沙坦治疗对循环单核细胞中 PPARγ 靶基因的调节作用。这些数据表明，血管紧张素 1 型受体阻滞剂替米沙坦可激活代谢综合征患者循环单核细胞中的 PPARγ。
