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血管紧张素Ⅱ受体阻滞剂氯沙坦对高血压患者单核细胞核心蛋白聚糖表达的影响。

Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients.

机构信息

Department of Internal Medicine, University of Messina, Messina, Italy.

出版信息

Clin Exp Pharmacol Physiol. 2010 Sep;37(9):933-8. doi: 10.1111/j.1440-1681.2010.05407.x. Epub 2010 May 24.

Abstract
  1. Recently, we demonstrated that biglycan (BGN) is increased in circulating monocyte cells from hypertensive patients and that angiotensin (Ang) II is able to increase BGN expression. The present study was designed to investigate the effects of treatment with the angiotensin AT(1) receptor antagonist losartan on monocyte BGN mRNA and protein expression in essential hypertension. 2. One hundred and twenty-six newly diagnosed hypertensive patients without additional risk factors for atherosclerosis and cardiovascular disease were treated with 100 mg losartan once daily for 6 months. Biglycan mRNA and protein expression was determined in monocytes isolated from peripheral blood before (T(0)) and after (T(1)) therapy. Plasma levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and high sensitivity C-reactive protein (hs-CRP) were also determined. In addition, BGN mRNA and protein expression was determined after the ex vivo addition of 1 micromol/L AngII to monocytes isolated from 20 randomly selected hypertensive patients. 3. Biglycan mRNA and protein expression, blood pressure and plasma levels of fibrinogen, IL-6, TNF-alpha and CRP were significantly lower at T(1) than at T(0). Variations in BGN expression were associated with inflammatory markers, but not directly with blood pressure. In AngII-stimulated monocytes, BGN mRNA and protein expression was significantly lower at T(1) that at T(0). Moreover, mean BGN mRNA expression in AngII-stimulated monocytes isolated from losartan-treated patients was similar to baseline expression in unstimulated monocytes from untreated patients. 4. The results of the present study show that losartan can reduce BGN expression in monocytes from hypertensive patients, without any linear association with blood pressure, suggesting that the effects of AngII on BGN expression in monocytes may be modulated, in part, by an AT(1) receptor blocker.
摘要
  1. 最近,我们证明了大软骨素聚糖(BGN)在高血压患者的循环单核细胞中增加,并且血管紧张素(Ang)II 能够增加 BGN 的表达。本研究旨在探讨血管紧张素 AT1 受体拮抗剂氯沙坦对原发性高血压患者单核细胞 BGNmRNA 和蛋白表达的影响。

  2. 126 例新诊断的高血压患者无动脉粥样硬化和心血管疾病的其他危险因素,给予氯沙坦 100mg 每日一次,治疗 6 个月。在治疗前(T0)和治疗后(T1)从外周血中分离单核细胞,测定大软骨素聚糖 mRNA 和蛋白表达。还测定了血浆白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和高敏 C 反应蛋白(hs-CRP)水平。此外,还测定了 20 例随机选择的高血压患者分离的单核细胞在体外加入 1μmol/L AngII 后大软骨素聚糖 mRNA 和蛋白的表达。

  3. T1 时大软骨素聚糖 mRNA 和蛋白表达、血压及血浆纤维蛋白原、IL-6、TNF-α和 CRP 水平均明显低于 T0。BGN 表达的变化与炎症标志物相关,但与血压无直接关系。在 AngII 刺激的单核细胞中,T1 时 BGNmRNA 和蛋白表达明显低于 T0。此外,在 AngII 刺激的单核细胞中,氯沙坦治疗患者的平均 BGNmRNA 表达与未经治疗患者未刺激单核细胞的基线表达相似。

  4. 本研究结果表明,氯沙坦可降低高血压患者单核细胞中的 BGN 表达,与血压无直接线性关系,提示 AngII 对单核细胞中 BGN 表达的影响可能部分受到 AT1 受体阻滞剂的调节。

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