6533b86cfe1ef96bd12c82d9

RESEARCH PRODUCT

Oxidative stress in cardiovascular disease: successful translation from bench to bedside?

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Over the last decades, sound evidence has been generated that oxidative stress is one of the most potent inductors of endothelial dysfunction and is involved at all stages of atherosclerotic plaque evolution.1,2 Experimental and animal models provide a clear association between the amount of oxidative challenge and reversible vascular dysfunction that can be observed before permanent alterations of the vessel wall occur. Article p 1367 Important for cardiovascular biology is the consumption of nitric oxide (NO) by reactive oxygen species. Endothelium relaxant factor is a central molecule in vascular homeostasis as a modulator of endothelial tone and reactivity.3 It is produced by NO synthases and exerts pleiotropic positive effects on the cardiovascular system.4 Oxidative modification of NO not only leads to reduced bioavailability but also produces the toxic oxidant peroxynitrite, which further aggravates the imbalance of protective and aggressive factors. Because oxidative stress centrally contributes to atherothrombosis, sustained efforts have been undertaken to translate this knowledge into the characterization and identification of biomarkers that enable detection of oxidative stress and allow improved risk stratification by integration into cardiovascular risk stratification models. Protagonists of oxidative stress have in common that they are highly active, short-lived agents that almost immediately react with surrounding molecules at the site of formation. However, oxidative species leave a detectable trace of modified oxidative products as is known for oxidized low-density lipoprotein at the site of atherosclerotic lesions. Among a multitude of oxidants that can be measured in vitro and in animal models, only comparatively few biomarkers have entered epidemiological investigations like homocysteine, nitrosated tyrosines, and the relatively unstable F2-isoprostanes, which have been related to endothelial function or cardiovascular outcome in cross-sectional and prospective investigations. Recently, myeloperoxidase, an endogenous generator of oxidants that is beneficial in host defense but detrimental for the …