Dworakowski Rafał, Walker Simon, Momin Aziz, Desai Jatin, El-Gamel Ahmed, Wendler Olaf, Kearney Mark T, Shah Ajay M
Cardiovascular Division, King's College London School of Medicine, London, United Kingdom.
J Am Coll Cardiol. 2008 Apr 8;51(14):1349-56. doi: 10.1016/j.jacc.2007.12.033.
We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure.
Vascular endothelial dysfunction in human heart failure contributes to increased tone, exercise limitation, and dysregulation of venous capacitance and vascular volume. The NADPH oxidases (Nox) are an important source of oxidative stress, but their role in the endothelial dysfunction of human heart failure remains unknown.
Endothelium-dependent and -independent vasorelaxation were assessed in saphenous vein segments obtained from consecutive patients with heart failure (n = 19) or normal left ventricular function (control; n = 35) undergoing coronary artery bypass graft. Saphenous vein superoxide production was measured by lucigenin-enhanced chemiluminescence and messenger ribonucleic acid expression of relevant transcripts quantified by real-time polymerase chain reaction.
Heart failure patients had significantly worse endothelial function than control subjects (15.2 +/- 3% vs. 40.5 +/- 8.4% relative relaxation; p < 0.05), elevated C-reactive protein (CRP) levels (8.6 +/- 2.7 mg/l vs. 2.6 +/- 0.4 mg/l; p < 0.05), over 2-fold higher NADPH-dependent superoxide generation (p < 0.05), and significantly higher expression of the Nox4 isoform and regulatory subunit p67phox. Superoxide levels were positively correlated with New York Heart Association functional class (r = 0.684; p < 0.05) and CRP (r = 0.501; p < 0.005; n = 32).
Venous endothelial dysfunction in human heart failure is associated with increased Nox-derived superoxide generation. Inflammatory mechanisms may be involved in the increased reactive oxygen species generation.
我们研究了还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶在人类心力衰竭内皮功能障碍中的作用。
人类心力衰竭中的血管内皮功能障碍会导致血管张力增加、运动受限以及静脉容量和血管容积调节异常。NADPH氧化酶（Nox）是氧化应激的重要来源，但其在人类心力衰竭内皮功能障碍中的作用尚不清楚。
对连续接受冠状动脉搭桥手术的心力衰竭患者（n = 19）或左心室功能正常的对照者（n = 35）的大隐静脉段进行内皮依赖性和非内皮依赖性血管舒张评估。通过荧光素增强化学发光法测量大隐静脉超氧化物生成，并通过实时聚合酶链反应对相关转录本的信使核糖核酸表达进行定量。
心力衰竭患者的内皮功能明显比对照者差（相对舒张率分别为15.2±3%和40.5±8.4%；p<0.05），C反应蛋白（CRP）水平升高（分别为8.6±2.7mg/l和2.6±0.4mg/l；p<0.05），NADPH依赖性超氧化物生成高出2倍以上（p<0.05），Nox4亚型和调节亚基p67phox的表达明显更高。超氧化物水平与纽约心脏协会功能分级呈正相关（r = 0.684；p<0.05），与CRP呈正相关（r = 0.501；p<0.00
