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生机制中起重要作用。血管内皮中活性氧（ROS）的增加最终阻碍了一氧化氮（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，并且在生理上可以检测到，因为内皮依赖的细胞内ROS水平的降低与糖尿病和高脂血症的发生机制有关，而糖尿病和高脂血症都是动脉粥样硬化的主要原因。因此，评估“氧化状态”显然与临床医学相关。然而，目前可用的大多数临床试验只是测量氧化废物。考虑到ROS水平是由产生和消除之间的平衡决定的，评估消除ROS的能力可能是氧化状态的主要决定因素，可能有助于评估个体对动脉粥样硬化性疾病的易感性。重点关注血红素加氧酶(HO)-1这一主要的应激防御机制之一，我们发现HO- 1mrna的上调能力与冠状动脉疾病的严重程度密切相关。此外，胁迫诱导的HO-1水平的个体差异与HO-1基因多态性有关。我们建议，临床使用HO-1表达谱作为抗氧化应激耐受性的指标可能与动脉粥样硬化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.