Cardiology Department, Heraklion University Hospital, Crete, Greece.
Am J Cardiol. 2011 Jan;107(1):59-63. doi: 10.1016/j.amjcard.2010.08.048.
Monocyte chemoattractant protein-1 (MCP-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) play a significant role in monocyte activation, vascular inflammation, and atherogenesis. Angiotensin receptor blockers and calcium channel blockers are antihypertensive drugs with established efficacy and a favorable safety profile. We investigated the effect of telmisartan--an angiotensin receptor blocker with PPAR-γ agonist activity--and amlodipine on the activation state of peripheral blood monocytes with respect to MCP-1 and PPAR-γ gene expression in hypertensives. We recruited 31 previously untreated patients with essential hypertension who were randomly assigned to receive treatment with telmisartan (n = 16) or amlodipine (n = 15). Blood samples were taken before and 3 months after therapy initiation. Mononuclear cells were isolated and mRNAs of MCP-1 and PPAR-γ were estimated by real-time quantitative reverse transcription-polymerase chain reaction each time. The 2 treatments decreased all blood pressure components significantly (p <0.001). In contrast, in the amlodipine group, MCP-1 gene expression was significantly downregulated after treatment with telmisartan (from 21.4 ± 20.5 to 8.1 ± 6.5, p = 0.009), whereas the amlodipine group did not show any significant change (12.5 ± 8.5 vs 17.6 ± 16.4, p = NS). In addition, PPAR-γ mRNA levels showed a significant increase in telmisartan-treated patients (from 20 ± 18.5 to 42.6 ± 36, p = 0.006) and no significant alterations in the amlodipine group (from 29.6 ± 42.5 to 24.2 ± 27.7, p = NS). In conclusion, treatment with telmisartan results in a significant attenuation of MCP-1 gene expression and an increase of PPAR-γ gene expression in peripheral monocytes in patients with essential hypertension. Our findings may provide new insights into the cardiovascular protection of telmisartan in hypertensives.
单核细胞趋化蛋白-1(MCP-1)和过氧化物酶体增殖物激活受体-γ(PPAR-γ)在单核细胞激活、血管炎症和动脉粥样硬化形成中起着重要作用。血管紧张素受体阻滞剂和钙通道阻滞剂是具有明确疗效和良好安全性的降压药物。我们研究了血管紧张素受体阻滞剂替米沙坦(具有 PPAR-γ激动剂活性)和氨氯地平对高血压患者外周血单核细胞激活状态的影响,以及它们对 MCP-1 和 PPAR-γ基因表达的影响。我们招募了 31 名未经治疗的原发性高血压患者,他们被随机分为替米沙坦组(n = 16)和氨氯地平组(n = 15)。在治疗开始前和 3 个月时采集血样。每次都分离单核细胞并通过实时定量逆转录聚合酶链反应估计 MCP-1 和 PPAR-γ 的 mRNA。两种治疗均显著降低所有血压成分(p <0.001)。相比之下,在氨氯地平组中,替米沙坦治疗后 MCP-1 基因表达显著下调(从 21.4 ± 20.5 降至 8.1 ± 6.5,p = 0.009),而氨氯地平组无明显变化(12.5 ± 8.5 与 17.6 ± 16.4,p = NS)。此外,替米沙坦治疗组 PPAR-γ mRNA 水平显著升高(从 20 ± 18.5 升至 42.6 ± 36,p = 0.006),而氨氯地平组无明显变化(从 29.6 ± 42.5 升至 24.2 ± 27.7,p = NS)。总之,替米沙坦治疗可显著降低原发性高血压患者外周血单核细胞中 MCP-1 基因表达,并增加 PPAR-γ 基因表达。我们的发现可能为替米沙坦在高血压患者中的心血管保护作用提供新的见解。