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雷米普利对成功修复主动脉缩窄的年轻血压正常受试者内皮功能、促炎细胞因子表达及黏附分子的影响:一项随机交叉研究。

Effects of ramipril on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young normotensive subjects with successfully repaired coarctation of aorta: a randomized cross-over study.

作者信息

Brili Stella, Tousoulis Dimitris, Antoniades Charalambos, Vasiliadou Carmen, Karali Maria, Papageorgiou Nikos, Ioakeimidis Nikos, Marinou Kyriakoula, Stefanadi Elli, Stefanadis Christodoulos

机构信息

First Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece.

出版信息

J Am Coll Cardiol. 2008 Feb 19;51(7):742-9. doi: 10.1016/j.jacc.2007.10.036.

Abstract

OBJECTIVES

The purpose of this study was to evaluate the effect of ramipril on endothelial function and inflammatory process in a group of normotensive subjects with successfully repaired coarctation of the aorta (SCR).

BACKGROUND

Subjects with SCR experience higher long-term cardiovascular risk as a result of the relapse of arterial hypertension or owing to nonreversible structural changes in the pre-coarctation arterial tree. These subjects experience endothelial dysfunction in the right forearm and appear to have elevated levels of proatherogenic inflammatory markers, even in the absence of arterial hypertension.

METHODS

Twenty young individuals age 27.3 +/- 2.4 years old with SCR 13.9 +/- 2.2 years previously, received ramipril 5 mg/day for 4 weeks in a randomized, cross-over, controlled trial. Endothelial function was evaluated in the right forearm by gauge-strain plethysmography, and serum levels of interleukin (IL)-1b, IL-6, soluble CD40 ligand (sCD40L), and soluble vascular cell adhesion molecule (sVCAM)-1 were determined by enzyme-linked immunosorbent assay.

RESULTS

Ramipril improved endothelial function (p < 0.001) and decreased the expression of proinflammatory cytokine IL-6 (p < 0.05) and sCD40L (p < 0.01). Furthermore, ramipril decreased serum levels of sVCAM-1 (p < 0.01) but failed to affect serum levels of C-reactive protein. These effects were independent of blood pressure lowering.

CONCLUSIONS

Ramipril reversed the impaired endothelial function and decreased the expression of proinflammatory cytokine IL-6, sCD40L, and adhesion molecules in normotensive subjects with SCR. These findings imply that ramipril treatment may have antiatherogenic effects in subjects with SCR, even in the absence of arterial hypertension.

摘要

目的

本研究旨在评估雷米普利对一组主动脉缩窄成功修复(SCR)的血压正常受试者的内皮功能和炎症过程的影响。

背景

由于动脉高血压复发或由于缩窄前动脉树的不可逆结构变化,SCR受试者面临更高的长期心血管风险。这些受试者右前臂存在内皮功能障碍,即使在没有动脉高血压的情况下,促动脉粥样硬化炎症标志物水平似乎也会升高。

方法

在一项随机、交叉、对照试验中,20名年龄为27.3±2.4岁、13.9±2.2年前接受过SCR的年轻个体,接受5mg/天雷米普利治疗4周。通过应变容积描记法评估右前臂的内皮功能,并通过酶联免疫吸附测定法测定白细胞介素(IL)-1β、IL-6、可溶性CD40配体(sCD40L)和可溶性血管细胞粘附分子(sVCAM)-1的血清水平。

结果

雷米普利改善了内皮功能(p<0.001),并降低了促炎细胞因子IL-6(p<0.05)和sCD40L(p<0.01)的表达。此外,雷米普利降低了sVCAM-1的血清水平(p<0.01),但未能影响C反应蛋白的血清水平。这些作用与血压降低无关。

结论

雷米普利逆转了SCR血压正常受试者受损的内皮功能,并降低了促炎细胞因子IL-6、sCD40L和粘附分子的表达。这些发现表明,即使在没有动脉高血压的情况下,雷米普利治疗对SCR受试者可能具有抗动脉粥样硬化作用。

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