Endothelial protection, AT(1) blockade and cholesterol-dependent oxidative stress - The EPAS trial

Article; Proceedings Paper

关键词: LOW-DENSITY-LIPOPROTEIN;    ANGIOTENSIN-CONVERTING ENZYME;    UP-REGULATION;    NAD(P)H OXIDASE;    OXIDIZED LDL;    RECEPTOR;    EXPRESSION;    PEPTIDE;    STATINS;    LOX-1;   

DOI  :  10.1161/CIRCULATIONAHA.105.001313

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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