© 2000 American Heart Association, Inc.
Editorials |
Mitochondrial Oxidative Stress in Heart Failure
"Oxygen Wastage" Revisited
From the Myocardial Biology Unit and Cardiovascular Division, Boston University Medical Center, and Boston University School of Medicine, Boston, Mass.
Correspondence to Wilson S. Colucci, MD, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wilson.colucci@bmc.org
Key Words: myocardium • free radicals • antioxidant
 |
Introduction |
|---|
There is growing evidence that oxidative stress is increased in myocardial failure and may contribute to the structural and functional changes that lead to disease progression. The report by Ide et al,1 in this issue of Circulation Research, provides the first direct measurement of increased oxidative stress in the myocardium of an animal model of heart failure. In this same model, the authors previously used electroparamagnetic resonance (EPR) with the O2- spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) to show that formation of superoxide anion was increased 2.8-fold in submitochondrial particles from failing (vs nonfailing) myocardium.2 The increase in DMPO spin signal was seen with NADH, but not succinate, as a substrate, suggesting that O2- was being formed by electron leakage at the level of the NADH-ubiquinone-reductase complex, or complex I. This view was supported by the finding that complex I activity was
50% lower in
the failing myocardium, suggesting a functional blockade of
the electron transport system. Because the isolation of
submitochondrial particles removes competing antioxidant enzymes, the
observed increase in DMPO spin signal was indicative of an increase in
gross (but not net) O2-
production and therefore was not necessarily indicative of
oxidative stress per se. Oxidative stress was suggested, however, by
the finding of increased lipid peroxidation products in the
myocardium of the animals with heart failure.
In the present study, Ide et al1 extend their earlier
observations by showing that the production of reactive oxygen
species (ROS) is increased in the failing
myocardium.2 By measuring the
This article has been cited by other articles:
 |
|
 |
|
  H. Tsutsui, S. Kinugawa, and S. Matsushima Mitochondrial oxidative stress and dysfunction in myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Sen, S. Khanna, and S. Roy Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart Cardiovasc Res, July 15, 2006; 71(2): 280 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Heinzel, Y. Luo, G. Dodoni, K. Boengler, F. Petrat, F. Di Lisa, H. de Groot, R. Schulz, and G. Heusch Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes Cardiovasc Res, July 15, 2006; 71(2): 374 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Cucoranu, R. Clempus, A. Dikalova, P. J. Phelan, S. Ariyan, S. Dikalov, and D. Sorescu NAD(P)H Oxidase 4 Mediates Transforming Growth Factor-{beta}1-Induced Differentiation of Cardiac Fibroblasts Into Myofibroblasts Circ. Res., October 28, 2005; 97(9): 900 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Castro, J. L. Vukasovic, M. Chiong, G. Diaz-Araya, H. Alcaino, M. Copaja, R. Valenzuela, D. Greig, O. Perez, R. Corbalan, et al. Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure Eur J Heart Fail, October 1, 2005; 7(6): 1033 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lowenstein Exogenous Thioredoxin Reduces Inflammation in Autoimmune Myocarditis Circulation, September 7, 2004; 110(10): 1178 - 1179. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Coronella-Wood, J. Terrand, H. Sun, and Q. M. Chen c-Fos Phosphorylation Induced by H2O2 Prevents Proteasomal Degradation of c-Fos in Cardiomyocytes J. Biol. Chem., August 6, 2004; 279(32): 33567 - 33574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Yeh, J.-H. S. Pang, Y.-C. Wu, Y.-C. Wang, J.-J. Chu, and P. J. Lin Differential-Display Polymerase Chain Reaction Identifies Nicotinamide Adenine Dinucleotide-Ubiquinone Oxidoreductase as an Ischemia/Reperfusion-Regulated Gene in Cardiomyocytes Chest, January 1, 2004; 125(1): 228 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Ahokas, K. J. Warrington, I. C. Gerling, Y. Sun, L. A. Wodi, P. A. Herring, L. Lu, S. K. Bhattacharya, A. E. Postlethwaite, and K. T. Weber Aldosteronism and Peripheral Blood Mononuclear Cell Activation: A Neuroendocrine-Immune Interface Circ. Res., November 14, 2003; 93 (10): e124 - e135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez-Porcel, L. O Lerman, D. R Holmes Jr., D. Richardson, C. Napoli, and A. Lerman Chronic antioxidant supplementation attenuates nuclear factor-{kappa}B activation and preserves endothelial function in hypercholesterolemic pigs Cardiovasc Res, March 1, 2002; 53(4): 1010 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsutsui, T. Ide, T. Shiomi, D. Kang, S. Hayashidani, N. Suematsu, J. Wen, H. Utsumi, N. Hamasaki, and A. Takeshita 8-Oxo-dGTPase, Which Prevents Oxidative Stress-Induced DNA Damage, Increases in the Mitochondria From Failing Hearts Circulation, December 11, 2001; 104(24): 2883 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shite, F. Qin, W. Mao, H. Kawai, S. Y. Stevens, and C.-s. Liang Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction in tachycardia-induced cardiomyopathy J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1734 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Schimke, J. Muller, F. Priem, I. Kruse, B. Schon, J. Stein, R. Kunze, G. Wallukat, and R. Hetzer Decreased oxidative stress in patients with idiopathic dilated cardiomyopathy one year after immunoglobulin adsorption J. Am. Coll. Cardiol., July 1, 2001; 38(1): 178 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ide, H. Tsutsui, S. Hayashidani, D. Kang, N. Suematsu, K.-i. Nakamura, H. Utsumi, N. Hamasaki, and A. Takeshita Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction Circ. Res., March 16, 2001; 88(5): 529 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Givertz, D. B. Sawyer, and W. S. Colucci Antioxidants and Myocardial Contractility : Illuminating the "Dark Side" of {{beta}}-Adrenergic Receptor Activation? Circulation, February 13, 2001; 103(6): 782 - 783. [Full Text] [PDF]
|
|
|
|
|
|
G. S. Nelson, R. D. Berger, B. J. Fetics, M. Talbot, J. C. Spinelli, J. M. Hare, and D. A. Kass Left Ventricular or Biventricular Pacing Improves Cardiac Function at Diminished Energy Cost in Patients With Dilated Cardiomyopathy and Left Bundle-Branch Block Circulation, December 19, 2000; 102(25): 3053 - 3059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinugawa, H. Tsutsui, S. Hayashidani, T. Ide, N. Suematsu, S. Satoh, H. Utsumi, and A. Takeshita Treatment With Dimethylthiourea Prevents Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction in Mice : Role of Oxidative Stress Circ. Res., September 1, 2000; 87(5): 392 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sam, D. B. Sawyer, Z. Xie, D. L.F. Chang, S. Ngoy, D. A. Brenner, D. A. Siwik, K. Singh, C. S. Apstein, and W. S. Colucci Mice Lacking Inducible Nitric Oxide Synthase Have Improved Left Ventricular Contractile Function and Reduced Apoptotic Cell Death Late After Myocardial Infarction Circ. Res., August 17, 2001; 89(4): 351 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Pimentel, J. K. Amin, L. Xiao, T. Miller, J. Viereck, J. Oliver-Krasinski, R. Baliga, J. Wang, D. A. Siwik, K. Singh, et al. Reactive Oxygen Species Mediate Amplitude-Dependent Hypertrophic and Apoptotic Responses to Mechanical Stretch in Cardiac Myocytes Circ. Res., August 31, 2001; 89(5): 453 - 460. [Abstract] [Full Text] [PDF]
|
|