Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress -: The EPAS trial
Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress -: The EPAS trial
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DOI：
10.1161/circulationaha.105.001313
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发表时间：
2006-07-04
期刊：
影响因子：
37.8
通讯作者：
Hambrecht, Rainer
中科院分区：
文献类型：
--
作者：
Morawietz, Henning;Erbs, Sandra;Hambrecht, Rainer
背景-他汀类药物和血管紧张素1型(AT1)受体阻滞剂可降低心血管死亡率和发病率。在内皮保护、AT1拮抗剂和胆固醇依赖的氧化应激(EPAS)试验中，检测了单独或联合应用他汀类和AT1受体阻滞剂对冠心病患者动脉抗动脉粥样硬化和致动脉粥样硬化基因的内皮表达和内皮功能的影响。方法和结果：60例接受选择性冠状动脉旁路移植(CABG)的稳定性冠心病患者在手术前4周随机分为：(A)不抑制肾素-血管紧张素系统或他汀类药物的对照组；(B)他汀类药物(普伐他汀40 mg/d)；(C)AT(1)阻滞剂(伊贝沙坦150 mg/d)；或(D)他汀类药物和AT1受体阻滞剂按相同剂量联合应用。主要终点是对抗动脉粥样硬化内皮细胞表达商Q的先验调节，包括内皮型一氧化氮合酶和C型利钠肽的mRNA表达(通过实时聚合酶链式反应以任意单位测量)，除以经冠状动脉旁路手术获得的左内乳动脉活检组织中氧化型低密度脂蛋白受体LOX-1和NAD(P)H氧化酶亚单位gp91Phox的表达；49名患者完成了研究。与对照组相比，他汀类药物治疗使LNQ从3.2+/-0.4显著增加到4.4+/-0.4。在(1)封锁时，LNQ有增加到4.2+/-0.5的趋势。联合应用他汀类药物和AT1阻滞剂可使LNQ进一步增加至5.1+/-0.6，但两种疗法在LNQ中的交互作用并不显著。此外，术前应用他汀类药物、AT1阻滞剂及其联合治疗可改善乳内动脉环内皮细胞的功能。结论他汀类药物和AT1阻滞剂单独及联合应用可提高抗动脉粥样硬化血管内皮细胞的表达商数和内皮功能。
Background-Statins and angiotensin type 1 (AT1) receptor blockers reduce cardiovascular mortality and morbidity. In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, impact of independent or combined statin and AT1 receptor blocker therapy on endothelial expression of anti-atherosclerotic and proathero-sclerotic genes and endothelial function in arteries of patients with coronary artery disease were tested.Methods and Results-Sixty patients with stable coronary artery disease undergoing elective coronary artery bypass grafting (CABG) surgery were randomized 4 weeks before surgery to: (A) control without inhibition of renin-angiotensin system or statin; (B) statin (pravastatin 40 mg/d); (C) AT(1) blockade (irbesartan 150 mg/d); or (D) combination of statin and AT1 blocker in same dosages. Primary end point was a priori therapy- dependent regulation of an anti-atherosclerotic endothelial expression quotient Q including mRNA expression (in arbitrary units measured by real-time polymerase chain reaction) of endothelial nitric oxide synthase and C-type natriuretic peptide, divided by expression of oxidized low-density lipoprotein receptor LOX-1 and NAD(P)H oxidase subunit gp91phox in left internal mammary arteries biopsies obtained by CABG surgery; 49 patients completed the study. Statin therapy increased lnQ from 3.2 +/- 0.4 to 4.4 +/- 0.4 significantly versus control. AT(1) blockade showed a trend to increase lnQ to 4.2 +/- 0.5. Combination of statin and AT1 blocker further increased lnQ to 5.1 +/- 0.6, but a putative interaction of both therapies in lnQ was not significant. Furthermore, preoperative therapy with statin, AT1 blocker and their combination improved endothelial function in internal mammary artery rings.Conclusions-Statin and AT1 blocker therapy independently and in combination improve an anti-atherosclerotic endothelial expression quotient and endothelial function.