Evaluating Oxidative Stress in Human Cardiovascular Disease: Methodological Aspects and Considerations

Abstract

Oxidative stress is a key feature in atherogenesis, since reactive oxygen species (ROS) are involved in all stages of the disease, from endothelial dysfunction to atheromatic plaque formation and rupture. It is therefore important to identify reliable biomarkers allowing us to monitor vascular oxidative stress status. These may lead to improved understanding of disease pathogenesis and development of new therapeutic strategies.Measurement of circulating biomarkers of oxidative stress is challenging, since circulation usually behaves as a separate compartment to the individual structures of the vascular wall. However, measurement of stable products released by the reaction of ROS and vascular/circulating molecular structures is a particularly popular approach. Serum lipid hydroperoxides, plasma malondialdehyde or urine F2-isoprostanes are widely used and have a prognostic value in cardiovascular disease.Quantification of oxidative stress at a tissue level is much more accurate. Various chemiluminescence and high performance liquid chromatography assays have been developed over the last few years, and some of them are extremely accurate and specific. Electron spin resonance spectroscopy and micro-electrode assays able to detect ROS directly are also widely used.In conclusion, measurement of circulating biomarkers of oxidative stress is valuable, and some of them appear to have predictive value in cardiovascular disease. However, these biomarkers do not necessarily reflect intravascular oxidative stress and therefore cannot be used as therapeutic targets or markers to monitor pharmacological treatments in clinical settings. Measurement of vascular oxidative stress status is still the only reliable way to evaluate the involvement of oxidative stress in atherogenesis.

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

“…The activity of vascular NADPH oxidase, a major source of O 2 _ 2 , is increased in patients with type 2 diabetes (2,25,26), a finding replicated in our cohort. Although NADPH oxidase is a major source of O 2 _ 2 in the human body, estimating its activity directly in the human vascular wall is challenging, and any indirect estimation by measuring circulating biomarkers of oxidative stress is unreliable (27). We now demonstrate that systemic oxidative stress (characterized by plasma MDA or 4-HNE levels) is not related to NADPH oxidase activity in the human arterial wall, suggesting that local 2 generation, irrespective of the presence of type 2 diabetes (T2D, n = 4; no T2D, n = 5).…”

Oxidative Stress and Lipid Peroxidation – A Lipid Metabolism Dysfunction

“…The anion produced by macrophages and endothelial cells induces conformational changes of receptors on the LDL lipoprotein surface, allowing their recognition and involvement in atherogenesis [10,12].…”

“…Much effort was further directed towards identification of factors that influence the susceptibility of LDL particles to oxidation. Among these, the presence of small dense LDS particles, of preformed lipid peroxides, as well as glycation or binding of LDLs to proteoglycans were proven to facilitate oxidation [12].…”

Paradoxical decrease in isoprostane and increase in superoxide dismutase following CPAP withdrawal in OSA

“…The "unexpected" results of our randomised and controlled interventional 2-week study are clear, and the actual assay results not in our view "questionable". The most important limitation we fully acknowledge in this (and all other clinical trials using systemic oxidative stress as a readout), is the absence of any reliable circulating or urinary biomarkers of oxidative stress that accurately describe tissue oxidation [6,7]. In the OSA model, for example, oxidation in the lung tissue may be completely different to systemic oxidation in the cardiovascular system or the kidneys, and this may also explain the discrepancy between the various studies.…”