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Statins and the Role of Nitric Oxide in Chronic Heart Failure

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Abstract

Endothelial dysfunction plays an important role in a number of cardiovascular diseases. An important pathogenetic factor for the development of endothelial dysfunction is lack of nitric oxide (NO), which is a potent endothelium-derived vasodilating substance. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), originally designed to lower plasma cholesterol levels, seem to ameliorate endothelial dysfunction by a mechanism so far only partly understood. However, statins increase nitric oxide synthase activity. It has been speculated that this and other “side effects” of statin treatment are due to inhibition of Rho, an intracellular signalling protein that initiates Rho kinase transcription. Moreover, statins possess anti-inflammatory characteristics. Some statins have proven to lower plasma levels of C-reactive protein, which is induced by pro-inflammatory cytokines. Other statins have been demonstrated to directly inhibit pro-inflammatory cytokine induction. Finally, some data suggest that statins might be able to counterbalance an increased production of oxygen free radicals. Since chronic heart failure is accompanied not only by endothelial dysfunction, but also by pro-inflammatory cytokine activation and enhanced formation of oxygen free radicals, it is tempting to speculate that statins might be an ideal candidate to treat certain features of this disease. The doses needed to achieve the desired effects might be much lower than those needed to treat hypercholesterolemia.

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Authors and Affiliations

  1. Department of Clinical Cardiology, National Heart & Lung Institute, Imperial College, School of Medicine, London, UK

    Stephan von Haehling & Stefan D. Anker

  2. Franz Volhard Klinik (Charité, Campus Berlin-Buch) at Max Delbrück Centrum for Molecular Medicine, Berlin, Germany

    Stephan von Haehling & Stefan D. Anker

  3. Institute of Applied Physiology, Albert-Ludwigs University, Freiburg, Germany

    Eberhard Bassenge

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von Haehling, S., Anker, S.D. & Bassenge, E. Statins and the Role of Nitric Oxide in Chronic Heart Failure. Heart Fail Rev 8, 99–106 (2003). https://doi.org/10.1023/A:1022103222857

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