Madamanchi Nageswara R, Vendrov Aleksandr, Runge Marschall S
Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill 27599-7005, USA.
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):29-38. doi: 10.1161/01.ATV.0000150649.39934.13. Epub 2004 Nov 11.
Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases (CVD). These ROS can be released from nicotinamide adenine dinucleotide (phosphate) oxidase, xanthine oxidase, lipoxygenase, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis: from the initiation of fatty streak development through lesion progress to ultimate plaque rupture. Various animal models of oxidative stress support the notion that ROS have a causal role in atherosclerosis and other cardiovascular diseases. Human investigations also support the oxidative stress hypothesis of atherosclerosis. Oxidative stress is the unifying mechanism for many CVD risk factors, which additionally supports its central role in CVD. Despite the demonstrated role of antioxidants in cellular and animal studies, the ineffectiveness of antioxidants in reducing cardiovascular death and morbidity in clinical trials has led many investigators to question the importance of oxidative stress in human atherosclerosis. Others have argued that the prime factor for the mixed outcomes from using antioxidants to prevent CVD may be the lack of specific and sensitive biomarkers by which to assess the oxidative stress phenotypes underlying CVD. A better understanding of the complexity of cellular redox reactions, development of a new class of antioxidants targeted to specific subcellular locales, and the phenotype-genotype linkage analysis for oxidative stress will likely be avenues for future research in this area as we move toward the broader use of pharmacological and regenerative therapies in the treatment and prevention of CVD.
越来越多的证据表明，在病理生理条件下，活性氧（ROS）的慢性和急性过量产生在心血管疾病（CVD）的发展中起着不可或缺的作用。这些ROS可从烟酰胺腺嘌呤二核苷酸（磷酸）氧化酶、黄嘌呤氧化酶、脂氧合酶、线粒体或血管细胞中一氧化氮合酶的解偶联中释放出来。ROS介导了动脉粥样硬化形成过程中血管炎症的各种信号通路：从脂肪条纹发展的起始到病变进展直至最终斑块破裂。各种氧化应激动物模型支持了ROS在动脉粥样硬化和其他心血管疾病中起因果作用的观点。人体研究也支持动脉粥样硬化的氧化应激假说。氧化应激是许多CVD危险因素的统一机制，这进一步支持了其在CVD中的核心作用。尽管抗氧化剂在细胞和动物研究中已显示出作用，但抗氧化剂在临床试验中未能有效降低心血管疾病的死亡率和发病率，这使得许多研究人员质疑氧化应激在人类动脉粥样硬化中的重要性。其他人则认为，使用抗氧化剂预防CVD产生混合结果的主要因素可能是缺乏评估CVD潜在氧化应激表型的特异性和敏感性生物标志物。随着我们朝着在CVD的治疗和预防中更广泛地使用药物和再生疗法迈进，更好地理解细胞氧化还原反应的复杂性、开发针对特定亚细胞区域的新型抗氧化剂以及氧化应激的表型-基因型连锁分析可能是该领域未来研究的途径。
