Recent Patents on Oxidative Stress-Related Biomarkers in Chronic Heart Failure: The Central Role of Endothelium and Myeloperoxidase
Rita Anzalone, Melania Lo Iacono, Antonino Di Stefano, Pantaleo Giannuzzi, Felicia Farina and Giampiero La Rocca
Affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Via del Vespro 129, Palermo, PA 90127, Italy.
Keywords: Chronic heart failure, coronary artery disease, diagnostic markers, endothelial dysfunction, endothelium, myeloperoxidase,
oxidative stress, prognostic biomarkers, serum assays.
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.
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