[Frontiers in Bioscience 14, 2230-2237, January 1, 2009]

Role of oxidative and nitrosative stress biomarkers in chronic heart failure

Ermanno Eleuteri1, Francesca Magno1,2, Isabella Gnemmi1, Marco Carbone1,2, Marilena Colombo1, Giampiero La Rocca2, Rita Anzalone2, Francesco Tarro Genta1, Giovanni Zummo2, Antonino Di Stefano1, Pantaleo Giannuzzi1

1Cardiology Unit and Laboratory of Cytoimmunopathology, Fondazione Salvatore Maugeri, IRCCS, Via per Revislate 13, Veruno (NO), Italy, 2Human Anatomy Section, Department of Experimental Medicine, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy


1. Abstract
2. NO/redox imbalance, endothelial dysfunction and MPO activity
2.1. Oxidative/nitrosative stress: the role of radicals
3. Redox mechanisms in blood vessels: sources of ROS
3.1. Xanthine oxido-reductase
3.2. NOS enzymes
3.3. Mitochondrial damage
3.4. Haemoglobin (SNO synthase and heme-oxidase)
4. Endothelial dysfunction and CHF
5. Biomarkers of oxidative stress and inflammation
5.1. Myeloperoxidase
5.2. Interleukins
6. BNP and NT-pro-BNP
7. Nitrosative stress and its relationship with systemic inflammation in patients with CHF
8. Acknowledgments
9. References


In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pulmonary and peripheral vascular beds. In patients with moderate to severe forms of CHF, TNF-alpha leads to the formation of nitrotyrosine and consumption of nitric oxide by virtue of activation of myeloperoxidase. Further studies are required to better elucidate the complex interaction of oxidative stress, endothelial dysfunction and inflammatory activation in CHF. Such insights would likely lead to development of better strategies for the assessment of the disease severity by monitoring of new bio-humoral indices and better treatment approaches.