Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis
Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis
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DOI：
10.1080/00365510801930626
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Zilmer, Mihkel
中科院分区：
文献类型：
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作者：
Kals, Jaak;Kampus, Priit;Zilmer, Mihkel
炎症和氧化应激（OxS）在动脉粥样硬化中起关键作用；然而，它们之间的因果关系尚不完全清楚。炎症是动脉粥样硬化的主要过程，而OxS可能是炎症过程的副产物。因此，我们假设慢性全身性炎症在亚临床状态下影响内皮血管舒缩功能，而氧化修饰更多地参与动脉粥样硬化的结构硬化。我们研究的目的是验证这一假设。通过脉搏波分析无创地评估内皮功能和动脉硬度，并采集了39例外周动脉疾病患者和34例对照组的血液/尿液样本。患者内皮功能指数（EFI）显著降低，增强指数（AIx）显著升高，主动脉脉波速度（PWV）估测值升高，细胞间粘附分子-1 （ICAM-1）、高敏c反应蛋白、髓过氧化物酶和尿8-异前列腺素F-2a （F-2-IsoPs）升高。对照组EFI与ICAM-1呈负相关（R=-0.44, p=0.009），而患者无相关。增强指数和估计主动脉PWV仅在患者中与F-2-IsoPs相关（R=0.5, p=0.001； R=-0.43, p=0.006）。在控制了潜在的混杂因素后，这些关联仍然显著。研究表明，在亚临床状态下，内皮血管舒缩能力的损害受炎症程度的影响，而动脉硬化则由动脉粥样硬化中氧化修饰的水平决定。
Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however, their causal relationship is not yet completely understood. Much attention has been given to the possibility that inflammation is a primary process of atherosclerosis and that OxS may be a by-product of the inflammatory process. We hypothesized, accordingly, that chronic systemic inflammation affects endothelial vasomotor function in the subclinical condition, whereas oxidative modifications are more involved in the structural stiffening of the arteries in atherosclerosis. The aim of our study was to test this hypothesis. Endothelial function and arterial stiffness were assessed non-invasively by pulse wave analysis, and blood/urinary samples were taken in 39 patients with peripheral arterial disease as well as in 34 controls. The patients showed significantly reduced endothelial function index (EFI) and increased augmentation index (AIx), as well as higher estimated aortic pulse wave velocity (PWV) and elevated values of the intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein, myeloperoxidase and urinary 8-iso-prostaglandin F-2a (F-2-IsoPs). There was an inverse association between EFI and ICAM-1 (R=-0.44, p=0.009) in the controls, but not in the patients. Augmentation index and estimated aortic PWV correlated with F-2-IsoPs only in the patients (R=0.5, p=0.001; R=-0.43, p=0.006, respectively). After controlling for potential confounders, these associations remained significant. The study demonstrates that impairment of endothelial vasomotor capacity is affected by degree of inflammation in the subclinical condition, whereas arterial stiffening is determined by level of oxidative modifications in atherosclerosis.