Assessment of tolerability against oxidative stress based on the inducible capacity of heme oxygenase-1

过度氧化应激在动脉粥样硬化的发病机制中起着重要作用。血管内皮细胞内活性氧香料(ROS)的增多最终会阻碍一氧化氮(NO)的血管扩张和细胞保护作用。这种情况被认为是动脉粥样硬化的早期特征，生理上可检测到的内皮依赖性降低和细胞内ROS水平的升高参与了糖尿病和高脂血症的发病机制，所有这些都是动脉粥样硬化的主要原因，因此，“氧化状态”的评估显然与临床医学有关。然而，目前可用的大多数临床测试只是测量氧化废物。考虑到ROS水平由产生和消除之间的平衡决定，对ROS清除能力的评估可能是氧化状态的主要决定因素，并可能有助于评估个体对动脉粥样硬化性疾病的易感性。针对主要的应激防御机制之一的血红素氧合酶(HO)-1，我们发现上调HO-1mRNA的能力与冠状动脉疾病的严重程度密切相关。此外，应激诱导的HO-1水平的个体差异由HO-1基因多态性决定。我们认为，临床使用HO-1表达谱作为对氧化应激耐受性的衡量标准，可能与动脉粥样硬化性疾病的早期诊断有关。

Excessive oxidative stress plays an important role in the mechanism of atherosclerosis. Increased revel of reactive oxygen spices (ROS) within vascular endothelium eventually impedes the vasodilative and cytoprotective actions of nitric oxide (NO). Such a condition is considered to be an early, feature of atherosclerosis, and physiologically detectable as a decrease in endothelium dependent Increased intracellular ROS levels are involved in the mechanisms of diabetes and hyperlipidemia, all of which are major of atherosclerosis Therefore, an assessment of "oxidative status" is obviously relevant to clinical medicine. However, most of the currently available clinical tests are just measuring oxidized wastes. Considering that ROS level is determined by the balance between production and elimination, an assessment of the ability to eliminate ROS may be a major determinant of oxidative state and may be useful to assess an individual susceptibility to atherosclerotic diseases. Focusing on heme oxygenase (HO)-1, one of the major stress defense mechanisms, we found that the capacity to upregulate HO-1mRNA is tightly associated with the severity of coronary artery disease. Furthermore, the individual difference in the stress-induced HO-1 levels was determined by HO-1 gene polymorphism. We propose that clinical use of HO-1 expression profile as a measure for tolerability against oxidative stress may be relevant to early diagnosis of atherosclerotic diseases.