II Medizinische Klinik für Kardiologie/Angiologie, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Eur Heart J. 2010 Nov;31(22):2741-8. doi: 10.1093/eurheartj/ehq396. Epub 2010 Oct 25.
An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing direct structural damage and by causing further ROS production. Despite this sound biological rationale and a number of pre-clinical and clinical lines of evidence, studies testing the effects of classical antioxidants such as vitamin C, vitamin E, or folic acid in combination with vitamin E have been disappointing. Rather, substances such as statins, angiotensin-converting enzyme inhibitors, or AT1-receptor blockers, which possess indirect antioxidant properties mediated by the stimulation of NO production and simultaneous inhibition of superoxide production (e.g. from the NADPH oxidase), have been shown to improve vascular function in pre-clinical and clinical studies and to reduce the incidence of cardiovascular events in patients with cardiovascular disease. Today, oxidative stress remains an attractive target for cardiovascular prevention and therapy. However, a deeper understanding of its source, and of its role in vascular pathology, is necessary before new trials are attempted.
活性氧（ROS）的异常产生以及随后导致血管中一氧化氮（NO）生物利用度降低，长期以来一直被认为是多种心血管危险因素（如高胆固醇血症、糖尿病、慢性吸烟、代谢综合征和高血压）导致内皮功能障碍的共同发病机制。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶、线粒体来源或黄嘌呤氧化酶产生的超氧阴离子可能与 NO 反应，从而导致过氧亚硝酸盐的过度形成，而过氧亚硝酸盐是一种活性氮物种，通过直接造成结构损伤和引起进一步的 ROS 产生，已被证明可加速动脉粥样硬化进程。尽管这一生物学理论基础合理，且有大量临床前和临床证据，但测试经典抗氧化剂（如维生素 C、维生素 E 或叶酸与维生素 E 的联合应用）效果的研究结果却令人失望。相反，某些物质如他汀类药物、血管紧张素转换酶抑制剂或 AT1 受体阻滞剂，具有通过刺激 NO 产生和同时抑制超氧阴离子产生（例如来自 NADPH 氧化酶）介导的间接抗氧化特性，已被证明可改善临床前和临床研究中的血管功能，并降低心血管疾病患者心血管事件的发生率。如今，氧化应激仍然是心血管预防和治疗的一个有吸引力的靶点。然而，在尝试新试验之前，有必要更深入地了解其来源及其在血管病理学中的作用。
