© 2004 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
New concepts in reactive oxygen species and cardiovascular reperfusion physiology
Emergency Resuscitation Center, Section of Emergency Medicine, Department of Medicine MC5068, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA
* Tel.: +1-773-702-2139; fax: +1-773-702-3135. lbecker{at}medicine.bsd.uchicago.edu
Increasingly complex behavior of free radicals and reactive oxygen species (ROS) are noted within biological systems. Classically free radicals and ROS were considered injurious, however current mechanisms describe both protective and deleterious effects. A burst of ROS has been well described with the first moments of reperfusion and is associated with injury. However ROS can also be protective as signal preconditioning protection and induce stress responses that lead to survival. ROS generation is appreciated to occur during ischemia despite the low oxygen tension, from a likely mitochondria source, and ROS-induced ROS release may amplify its signal. The burst of ROS seen during reperfusion may originate from a different cellular source than during ischemia and is not yet fully identified. ROS and cellular redox conditions regulate a large number of vital pathways (energy metabolism, survival/stress responses, apoptosis, inflammatory response, oxygen sensing, etc). While cellular systems may demonstrate reperfusion injury, whole organ and animal models continue to report contradictory results on reperfusion injury and the role of antioxidants as a therapy. Collectively, these data may offer insight into why clinical trials of antioxidants have had such mixed and mostly negative results. Future antioxidant therapies are likely to be effective but they must become: more specific for site of action, not have deleterious effects on other signaling pathways, be targeted to a specific reactive oxygen species or cellular compartment, and be "time sensitive" so they deliver the correct therapy at precisely the correct time in ischemia and reperfusion.
KEYWORDS Reactive oxygen species; ROS; Oxidant stress; Cell signaling; Reperfusion injury; Free radicals; Cardioprotection
Time for primary review 29 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Tsukamoto, T. Minamino, and M. Kitakaze Functional alterations of cardiac proteasomes under physiological and pathological conditions Cardiovasc Res, September 4, 2009; (2009) cvp282v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dreger, K. Westphal, A. Weller, G. Baumann, V. Stangl, S. Meiners, and K. Stangl Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection Cardiovasc Res, July 15, 2009; 83(2): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Carriere, T. G. Ebrahimian, S. Dehez, N. Auge, C. Joffre, M. Andre, S. Arnal, M. Duriez, C. Barreau, E. Arnaud, et al. Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1093 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Zhou, L. Zhang, J. Xi, W. Tian, and Z. Xu Ethanol Prevents Oxidant-Induced Mitochondrial Permeability Transition Pore Opening in Cardiac Cells Alcohol Alcohol., January 1, 2009; 44(1): 20 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Chen, J. Chen, S. Rawale, S. Varadharaj, P. P. T. Kaumaya, J. L. Zweier, and Y.-R. Chen Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium J. Biol. Chem., October 10, 2008; 283(41): 27991 - 28003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Jaques-Robinson, R. Golfetti, S. S. Baliga, N. M. Hadzimichalis, and G. F. Merrill Acetaminophen Is Cardioprotective Against H2O2-Induced Injury In Vivo Experimental Biology and Medicine, October 1, 2008; 233(10): 1315 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hu, A. Dandapat, L. Sun, J. Chen, M. R. Marwali, F. Romeo, T. Sawamura, and J. L. Mehta LOX-1 deletion decreases collagen accumulation in atherosclerotic plaque in low-density lipoprotein receptor knockout mice fed a high-cholesterol diet Cardiovasc Res, July 15, 2008; 79(2): 287 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Huang, A. Karve, I. Shah, M. C. Bowers, D. J. DiPette, S. C. Supowit, and G. S. Abela Deletion of the mouse {alpha}-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1291 - H1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Chen, S. Moghaddas, C. L. Hoppel, and E. J. Lesnefsky Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria Am J Physiol Cell Physiol, February 1, 2008; 294(2): C460 - C466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aldakkak, D. F. Stowe, Q. Chen, E. J. Lesnefsky, and A. K.S. Camara Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release Cardiovasc Res, January 15, 2008; 77(2): 406 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. M. Kim, H. Kattach, C. Ratnatunga, R. Pillai, K. M. Channon, and B. Casadei Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 68 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-R. Chen, C.-L. Chen, D. R. Pfeiffer, and J. L. Zweier Mitochondrial Complex II in the Post-ischemic Heart: OXIDATIVE INJURY AND THE ROLE OF PROTEIN S-GLUTATHIONYLATION J. Biol. Chem., November 9, 2007; 282(45): 32640 - 32654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Blackstone A food's-eye view of the transition from basal metazoans to bilaterians Integr. Comp. Biol., November 1, 2007; 47(5): 724 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dandapat, C. Hu, L. Sun, and J. L. Mehta Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1 Dependent Redox-Sensitive Pathway Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2435 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hu, A. Dandapat, J. Chen, Y. Fujita, N. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, T. Sawamura, and J. L. Mehta LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion Cardiovasc Res, November 1, 2007; 76(2): 292 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tanaka-Esposito, Q. Chen, S. Moghaddas, and E. J. Lesnefsky Ischemic preconditioning does not protect via blockade of electron transport J Appl Physiol, August 1, 2007; 103(2): 623 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Penna, D. Mancardi, R. Rastaldo, G. Losano, and P. Pagliaro Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling Cardiovasc Res, July 1, 2007; 75(1): 168 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Davidson and M. R. Duchen Endothelial Mitochondria: Contributing to Vascular Function and Disease Circ. Res., April 27, 2007; 100(8): 1128 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zissimopoulos, N. Docrat, and F. A. Lai Redox Sensitivity of the Ryanodine Receptor Interaction with FK506-binding Protein J. Biol. Chem., March 9, 2007; 282(10): 6976 - 6983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Nam, K. Mani, L. Wu, C.-F. Peng, J. W. Calvert, R. S.-Y. Foo, B. Krishnamurthy, W. Miao, A. W. Ashton, D. J. Lefer, et al. The Apoptosis Inhibitor ARC Undergoes Ubiquitin-Proteasomal-mediated Degradation in Response to Death Stimuli: IDENTIFICATION OF A DEGRADATION-RESISTANT MUTANT J. Biol. Chem., February 23, 2007; 282(8): 5522 - 5528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chen, A. K. S. Camara, D. F. Stowe, C. L. Hoppel, and E. J. Lesnefsky Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion Am J Physiol Cell Physiol, January 1, 2007; 292(1): C137 - C147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Sharma, J. Sun, L. L. Howard, A. G. Williams Jr., and R. T. Mallet Oxidative stress reversibly inactivates myocardial enzymes during cardiac arrest Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H198 - H206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Kolar, J. Jezkova, P. Balkova, J. Breh, J. Neckar, F. Novak, O. Novakova, H. Tomasova, M. Srbova, B. Ost'adal, et al. Role of oxidative stress in PKC-{delta} upregulation and cardioprotection induced by chronic intermittent hypoxia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H224 - H230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Taylor, M. E. Olsen, and J. W. Starnes Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H601 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Stoner, T. L. Clanton, S. E. Aune, and M. G. Angelos O2 delivery and redox state are determinants of compartment-specific reactive O2 species in myocardial reperfusion Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H109 - H116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Chen, S. Moghaddas, C. L. Hoppel, and E. J. Lesnefsky Reversible Blockade of Electron Transport during Ischemia Protects Mitochondria and Decreases Myocardial Injury following Reperfusion J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1405 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. N. Kabir, J. E. Clark, M. Tanno, X. Cao, J. S. Hothersall, S. Dashnyam, D. A. Gorog, M. Bellahcene, M. J. Shattock, and M. S. Marber Cardioprotection initiated by reactive oxygen species is dependent on activation of PKC{varepsilon} Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1893 - H1899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Canton, A. Skyschally, R. Menabo, K. Boengler, P. Gres, R. Schulz, M. Haude, R. Erbel, F. Di Lisa, and G. Heusch Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization Eur. Heart J., April 1, 2006; 27(7): 875 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, M. Tong, S. Chinta, J. U. Raj, and Y. Gao Hypoxia-induced reactive oxygen species downregulate ETB receptor-mediated contraction of rat pulmonary arteries Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L570 - L578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Pachori, L. G. Melo, L. Zhang, S. D. Solomon, and V. J. Dzau Chronic Recurrent Myocardial Ischemic Injury Is Significantly Attenuated by Pre-Emptive Adeno-Associated Virus Heme Oxygenase-1 Gene Delivery J. Am. Coll. Cardiol., February 7, 2006; 47(3): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Petrosillo, N. Di Venosa, M. Pistolese, G. Casanova, E. Tiravanti, G. Colantuono, A. Federici, G. Paradies, and F. M. Ruggiero Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia- reperfusion: role of cardiolipin FASEB J, February 1, 2006; 20(2): 269 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukushima, S. R. Coppen, A. Varela-Carver, G. Brindley, K. Yamahara, P. Sarathchandra, M. H. Yacoub, and K. Suzuki Enhanced efficiency of superoxide dismutase-induced cardioprotection by retrograde intracoronary administration Cardiovasc Res, February 1, 2006; 69(2): 459 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, E. M. Alicot, I. Chiu, J. Li, N. Verna, T. Vorup-Jensen, B. Kessler, M. Shimaoka, R. Chan, D. Friend, et al. Identification of the target self-antigens in reperfusion injury J. Exp. Med., January 23, 2006; 203(1): 141 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chen, C. L. Hoppel, and E. J. Lesnefsky Blockade of Electron Transport before Cardiac Ischemia with the Reversible Inhibitor Amobarbital Protects Rat Heart Mitochondria J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 200 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuda, S. S. Davies, T. Nakajima, B.-H. Ong, S. Kupershmidt, J. Fessel, V. Amarnath, M. E. Anderson, P. A. Boyden, P. C. Viswanathan, et al. Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels Circ. Res., December 9, 2005; 97(12): 1262 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Napoli, S. Williams-Ignarro, F. de Nigris, G. de Rosa, L. O. Lerman, B. Farzati, A. Matarazzo, G. Sica, C. Botti, A. Fiore, et al. Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb PNAS, November 22, 2005; 102(47): 17202 - 17206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Obal, S. Dettwiler, C. Favoccia, H. Scharbatke, B. Preckel, and W. Schlack The Influence of Mitochondrial KATP-Channels in the Cardioprotection of Preconditioning and Postconditioning by Sevoflurane in the Rat In Vivo Anesth. Analg., November 1, 2005; 101(5): 1252 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Palfi, A. Toth, G. Kulcsar, K. Hanto, P. Deres, E. Bartha, R. Halmosi, E. Szabados, L. Czopf, T. Kalai, et al. The Role of Akt and Mitogen-Activated Protein Kinase Systems in the Protective Effect of Poly(ADP-Ribose) Polymerase Inhibition in Langendorff Perfused and in Isoproterenol-Damaged Rat Hearts J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 273 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chen, E. Einbinder, Q. Zhang, J. Hasday, C. W. Balke, and S. M. Scharf Oxidative Stress and Left Ventricular Function with Chronic Intermittent Hypoxia in Rats Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 915 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tang, Q. Hao, S. A. Rutherford, B. Low, and Z. J. Zhao Inactivation of Src Family Tyrosine Kinases by Reactive Oxygen Species in Vivo J. Biol. Chem., June 24, 2005; 280(25): 23918 - 23925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, L. Jia, T. Wang, W. Sun, S. Wu, and X. Wang Endogenous Calcitonin Gene-related Peptide Protects Human Alveolar Epithelial Cells through Protein Kinase C{epsilon} and Heat Shock Protein J. Biol. Chem., May 27, 2005; 280(21): 20325 - 20330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kimura, G.-X. Zhang, A. Nishiyama, T. Shokoji, L. Yao, Y.-Y. Fan, M. Rahman, T. Suzuki, H. Maeta, and Y. Abe Role of NAD(P)H Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Cardioprotection of Ischemic Reperfusion Injury by Angiotensin II Hypertension, May 1, 2005; 45(5): 860 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Choi, Y.-J. Jeong, Y.-J. Lee, H.-M. Kwon, and Y.-H. Kang (-)Epigallocatechin Gallate and Quercetin Enhance Survival Signaling in Response to Oxidant-Induced Human Endothelial Apoptosis J. Nutr., April 1, 2005; 135(4): 707 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Coller Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene? Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 658 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Weinberg, M. Scherrer-Crosbie, M. H. Picard, B. A. Nasseri, C. MacGillivray, J. Gannon, Q. Lian, K. D. Bloch, and R. T. Lee Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1802 - H1809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, K.-D. Schluter, E. A. Martinson, and H. M. Piper Which papers are most interesting to the readers of Cardiovascular Research? Information from download monitoring Cardiovasc Res, January 1, 2005; 65(1): 1 - 5. [Full Text] [PDF]
|
|
|
|
|
|
F. R Eberli Stunned myocardium--an unfinished puzzle Cardiovasc Res, August 1, 2004; 63(2): 189 - 191. [Full Text] [PDF]
|
|
|
|
|
|
I. Tritto and G. Ambrosio The multi-faceted behavior of nitric oxide in vascular "inflammation": catchy terminology or true phenomenon? Cardiovasc Res, July 1, 2004; 63(1): 1 - 4. [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado Myocardial reperfusion injury: a new view Cardiovasc Res, February 15, 2004; 61(3): 363 - 364. [Full Text] [PDF]
|
|