Recent Patents on Oxidative Stress-Related Biomarkers in Chronic Heart Failure: The Central Role of Endothelium and Myeloperoxidase

Endothelial cells are key modulators of multiple physiological processes, and their impairment may result in the generation of endothelial dysfunction and ultimately cardiovascular diseases. Under physiologic conditions, reactive oxygen and nitrogen mediators of endothelial cells act to propagate signals driven by different stimuli, by forming molecules with a longer half-life like hydrogen peroxide. Reactive oxygen species (ROS) are constantly produced as a consequence of aerobic metabolism. Under physiologic conditions, their tendency to cause oxidative damage is counterbalanced by the action of antioxidants or oxidant-scavenging enzymes. An imbalance in favour of oxidants leads to oxidative stress, which can result in cardiomyocyte apoptosis and reduced bioavailability of vascular nitric oxide (NO). Together, these processes may lead to altered vasodilatation of the coronary, pulmonary and peripheral vascular beds. Myeloperoxidase is a key enzyme, capable of impairing intracellular NO reservoirs as well as producing oxidized amino acids such as 3-chlorotyrosine or 3-nitrotyrosine. Recent literature data have shown that apart neutrophils, this enzyme may be expressed by other cell types, and remarkably by endothelial cells both in vitro and in vivo, as a consequence of the exposure to oxidative stress. In this review we analyze recent literature and patents related to the detection, quantification and role of myeloperoxidase as a biomarker in patients affected by chronic heart failure or other cardiovascular diseases. A particular focus is given to analytical approaches aimed to detect early signals of variations in ROS or related enzymes or their by-products, via serological or other low-invasivity assays. The developments in this field may constitute a key improvement of the ability to manage and treat patients suffering from CHF as well as allowing to elucidate the molecular mechanisms behind the clinical phenomena