Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition.
Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition.
复制标题
ACE 基因的插入-缺失多态性通过 ACE 抑制调节内皮功能障碍的可逆性。
DOI：
10.1161/01.cir.102.1.35
复制
发表时间：
2000
期刊：
影响因子：
37.8
通讯作者：
Quyyumi,AA
中科院分区：
文献类型：
--
作者：
Prasad,A;Narayanan,S;Husain,S;Padder,F;Waclawiw,M;Epstein,N;Quyyumi,AA
背景-本研究的目的是检测血管紧张素转换酶（ACE）抑制剂是否改善动脉粥样硬化及其危险因素患者的冠状动脉内皮功能障碍，以及这是否与ACE插入-缺失（I/D）多态性有关。方法和结果-在56例动脉粥样硬化及其危险因素患者中，我们研究了乙酰胆碱的内皮依赖性反应和硝普钠的内皮非依赖性功能，在用依那普利拉抑制ACE前后。依那普利拉不改变静息冠状动脉张力或硝普钠的血管舒张作用。然而，它加强了冠状动脉微血管和心外膜反应与乙酰胆碱;冠状动脉血流量增加82±7至90±8 mL/min（P=0.05）后，依那普利拉。多变量分析显示，内皮功能低下（P<0.001）和ACE基因型为DDorID（P=0.002）但I等位基因纯合子的患者改善最大。同样，乙酰胆碱介导的心外膜血管运动在最初收缩的节段（内皮功能障碍）中得到改善：依那普利拉后从-10.1 ±1%增加到-1.4 ±2%（P<0.001）。在用乙酰胆碱扩张（正常内皮功能障碍）的节段中未观察到增强。患者与D等位基因，高胆固醇血症，吸烟者（所有P <0.05）有更大的改善。结论急性ACE抑制改善冠状动脉心外膜和微血管内皮依赖性血管运动的患者动脉粥样硬化或其危险因素有内皮功能障碍和D等位基因的存在。
Background—The aim of this study was to examine whether angiotensin-converting enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to theACEinsertion-deletion(I/D)polymorphism.Methods and Results—In 56 patients with atherosclerosis or its risk factors, we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; coronary blood flow increased from 82±7 to 90±8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and those withACE DDorIDgenotypes (P=0.002) but not those homozygous for theIallele had the greatest improvement by multivariate analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted (endothelial dysfunction): from −10.1±1% to −1.4±2% (P<0.001) after enalaprilat. No augmentation was observed in segments that dilated (normal endothelial dysfunction) with acetylcholine. Patients with theDallele, hypercholesterolemia, and smokers (allP<0.05) had greater improvement.Conclusions—Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of theDallele.