source Mortensen, S. The effect of coenzyme Q 10 on morbidity and mortality in chronic heart failure. Burgoyne, J. Redox signaling in cardiac physiology and pathology. Oka, T. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature , — Lygate, C. Metabolic flux as a predictor of heart failure prognosis.
Hare, J. Impact of oxypurinol in patients with symptomatic heart failure. Ernster, L.
Biochemical, physiological and medical aspects of ubiquinone function. Acta , — McMurray, J. Coenzyme Q 10 , rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA controlled rosuvastatin multinational study in heart failure. O'Connor, C. JAMA , — Dai, D. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy.
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Reactive oxygen species ROS are important in normal cellular function and physiology. Oxidative stress is defined as an imbalance between the synthesis of reactive oxygen species ROS and their elimination by antioxidant defense systems, with a prevailing pro-oxidant status that results in macromolecular damage and disrupts cellular redox signaling. Xie et al. Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis. Healthy control subjects For ethical reasons a control group of patients receiving immunsuppressive medication could not be used. Oikonomou, G. Insights into the potential importance of selenium in heart failure.
International Journal of Cardiology Cardiovascular Research Experimental Cell Research Article metrics. Advanced search. There is widespread recognition of the role of oxidative stress in the pathogenesis of many diseases, including HF. ROS interfere with various processes that affect cardiac structure and function, contributing to apoptosis and mitochondrial dysfunction in cardiomyocytes, contractile dysfunction, myocardial fibrosis and hypertrophy, endothelial dysfunction and atherosclerosis. These effects are mainly mediated by inhibition of pro-oxidant enzymes such as Nox and by stimulation of the expression, activity and stability of e NO S.
In addition, statins stimulate other antioxidant enzymes and help control inflammatory processes. Statins thus have effects on various molecules that are central to both oxidative stress and inflammation, notably by stimulating the synthesis of epi-LXA 4 , which has pro-resolving, anti-inflammatory and antioxidant properties. Their antioxidant effects have been demonstrated in several cardiovascular conditions, including HF , CAD and AF , mainly in the early stages of these diseases Table Effects of statins in heart failure with reduced ejection fraction: non-randomized studies adapted from 6—8,69,85,8 With regard to the effects of statins in reducing cardiovascular events and mortality in HF , although various observational studies have shown reduced mortality with statin therapy, two large clinical trials — CORONA and GISSI- HF — did not demonstrate such a benefit.
Given the lack of consensus, further clinical trials are needed to clarify the clinical value of statins in subgroups of HF patients and its relation with their effects on redox state.. The authors declare that no experiments were performed on humans or animals for this study.. The authors declare that no patient data appear in this article.. The authors have no conflicts of interest to declare.. Rev Port Cardiol. Revista Portuguesa de Cardiologia English edition.
ISSN: Open Access Option. Previous article Next article. Issue 1. Pages January Download PDF. Corresponding author. This item has received. Under a Creative Commons license. Article information. Show more Show less. Table 1. Table 2. Effects of statins in heart failure: non-randomized observational studies adapted from6—8,84, Table 3. Effects of statins in heart failure with reduced ejection fraction: non-randomized studies adapted from6—8,69,85, In addition to decreasing cholesterol synthesis, statins interfere with the synthesis of isoprenoid intermediates, which may explain many of their pleiotropic properties, including their antioxidant effects.
The results of observational studies and clinical trials with statins in heart failure have not been consensual. It also examines current scientific evidence on the use of these drugs as a specific treatment for heart failure. List of abbreviations. American College of Cardiology. DNA damage-binding protein 2. European Society of Cardiology. N-terminal brain-type natriuretic peptide. New York Heart Association. Totally synthetic statins have different structures that may account for their solubility differences in water.
Figure 1. Figure 2. Pleiotropic effects of statins and associated molecular pathways. Figure 3. Effects of oxidative stress on endothelial nitric oxide synthase. Figure 4. Action of statins on endothelial nitric oxide synthase. Figure 5. Action of statins on nicotinamide adenine dinucleotide phosphate oxidase in endothelial cells. Figure 6. Statins and synthesis of epi-lipoxins: protective effects.
Figure 7. Effects of statins in heart failure with reduced ejection fraction: non-randomized studies adapted from 6—8,69,85,8 7. Mozaffarian, E. Benjamin, A. Go, et al. Heart disease and stroke statistics — update: a report from the American Heart Association. Circulation, , pp. Yancy, M. Jessup, B. Bozkurt, et al. J Am Coll Cardiol, 62 , pp. McMurray, S. Adamopoulos, S. Anker, et al. Eur J Heart Fail, 33 , pp. Nitroso-redox balance in the cardiovascular system. N Engl J Med, , pp. Tousoulis, E. Oikonomou, G. Siasos, et al.
Statins in heart failure—with preserved and reduced ejection fraction. An update. Pharmacol Ther, , pp. Bonsu, A. Kadirvelu, D.
Statins in heart failure: do we need another trial?. Vasc Health Risk Manag, 9 , pp. S Medline. Tang, G. Statin treatment for patients with heart failure. Nat Rev Cardiol, 7 , pp. Horwich, M. Hamilton, W. Maclellan, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure.
J Card Fail, 8 , pp. Liao, U. Annu Rev Pharmacol Toxicol, 45 , pp. Margaritis, K. Channon, C. Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid Redox Signal, 20 , pp. Am J Physiol Cell Physiol, , pp.
Sousa, J. Afonso, F. Carvalho, et al. Lipid peroxidation and antioxidants in arterial hypertension. Lipid peroxidation, pp. Tsutsui, S. Kinugawa, S. Kaludercic, A. Carpi, R. Menabo, et al. Biochim Biophys Acta, , pp. Tang, M. Brennan, K. Philip, et al. Plasma myeloperoxidase levels in patients with chronic heart failure. Am J Cardiol, 98 , pp. Brown, K.
Free Radic Biol Med, 47 , pp. Kuroda, J. J Cardiovasc Transl Res, 3 , pp. Octavia, H. Brunner-La Rocca, A. NADPH oxidase-dependent oxidative stress in the failing heart: from pathogenic roles to therapeutic approach. Free Radic Biol Med, 52 , pp. Kwok, C. Ma, S. Vascul Pharmacol, 58 , pp. Schramm, P. Matusik, G. Osmenda, et al. Vascul Pharmacol, 56 , pp. Yamamoto, K. Kataoka, H. Shintaku, et al. Novel mechanism and role of angiotensin II induced vascular endothelial injury in hypertensive diastolic heart failure.
Arterioscler Thromb Vasc Biol, 27 , pp. Manni, M. Zazzeri, C. Musilli, et al. Exposure of cardiomyocytes to angiotensin II induces over-activation of monoamine oxidase type A: implications in heart failure. Eur J Pharmacol, , pp. Villeneuve, C. Guilbeau-Frugier, P. Sicard, et al. Antioxid Redox Signal, 18 , pp. Carpi, T. Nagayama, et al. Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Reina-Couto, J.
Carvalho, M. Valente, et al. Impaired resolution of inflammation in human chronic heart failure. Eur J Clin Invest, 44 , pp. Haendeler, J. Hoffmann, A. Zeiher, et al. Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins.
Abraham, A. Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med, 39 , pp. Anti-oxidant properties of high-density lipoprotein and atherosclerosis. Clin Exp Pharmacol Physiol, 37 , pp. Sawyer, D. Siwik, L. Xiao, et al.
1. Am J Physiol Heart Circ Physiol. Dec;(6):H doi: / ajpheart Epub Sep Over the past several decades investigations in humans and animal models of heart failure have provided substantial evidence that oxidative stress is increased .
Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol, 34 , pp. Dieterich, U. Bieligk, K.
Beulich, et al. Gene expression of antioxidative enzymes in the human heart: increased expression of catalase in the end-stage failing heart. Baumer, M. Flesch, X. Wang, et al. Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy. J Mol Cell Cardiol, 32 , pp. Sam, D. Kerstetter, D.
Pimental, et al. Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium. J Card Fail, 11 , pp. De Lorgeril, P. Salen, M. Accominotti, et al. Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure.
Eur J Heart Fail, 3 , pp. Oxygen, oxidative stress, hypoxia, and heart failure.
J Clin Invest, , pp. Pacher, J. Beckman, L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev, 87 , pp. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med, 26 , pp. Rastaldo, P. Pagliaro, S. Cappello, et al. Life Sci, 81 , pp. Aoki, A. Nakano, S. Tanaka, et al. Fluvastatin upregulates endothelial nitric oxide synthase activity via enhancement of its phosphorylation and expression and via an increase in tetrahydrobiopterin in vascular endothelial cells.
Int J Cardiol, , pp. Hattori, N. Nakanishi, K. Akimoto, et al. Arterioscler Thromb Vasc Biol, 23 , pp. Ota, M. Eto, M. Kano, et al. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol, 30 , pp. Kosmidou, J. Moore, M.
Weber, et al. Wang, Z. Xu, I. Kitajima, et al. Effects of different statins on endothelial nitric oxide synthase and AKT phosphorylation in endothelial cells. Sun, T. Lee, M. Zhu, et al. Statins activate AMP-activated protein kinase in vitro and in vivo. Brouet, P. Sonveaux, C.
Dessy, et al. Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res, 89 , pp. Mineo, P. Adv Exp Med Biol, , pp. Carnevale, P. Pignatelli, S. Di Santo, et al. Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients. Atherosclerosis, , pp. Kanugula, P. Gollavilli, S. Vasamsetti, et al. Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.
FEBS J, ,. Schupp, U. Schmid, A. Heidland, et al. Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Grosser, K. Erdmann, A.
Hemmerle, et al. Rosuvastatin upregulates the antioxidant defense protein heme oxygenase Biochem Biophys Res Commun, , pp. Nagila, T. Permpongpaiboon, S. Tantrarongroj, et al. Effect of atorvastatin on paraoxonase1 PON1 and oxidative status. Pharmacol Rep, 61 , pp. Khaper, S. Bryan, S. Dhingra, et al.
Targeting the vicious inflammation-oxidative stress cycle for the management of heart failure. Antioxid Redox Signal, 13 , pp. Causal link between oxidative stress, inflammation, and hypertension. Iran J Kidney Dis, 2 , pp. Zenz, R. Eferl, C. Scheinecker, et al. Arthritis Res Ther, 10 , pp. Corda, C. Laplace, E. Vicaut, et al. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Kaur, G. Dhaunsi, R.
Interleukin-1 and nitric oxide increase NADPH oxidase activity in human coronary artery smooth muscle cells. Med Princ Pract, 13 , pp. Anatoliotakis, S. Deftereos, G. Bouras, et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease.
Curr Top Med Chem, 13 , pp. Kumar, W. Statins downregulate myeloperoxidase gene expression in macrophages. Madrigal-Matute, J. Lindholt, C. Fernandez-Garcia, et al. Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis. Lee, Y. Koh, H. Park, et al. Spatial and temporal expression, and statin responsiveness of galectin-1 and galectin-3 in murine atherosclerosis.
Korean Circ J, 43 , pp. Spite, C. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ Res, , pp. Birnbaum, Y. Ye, Y. Lin, et al. Augmentation of myocardial production of epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat. Planaguma, M.