© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Peroxynitrite-induced myocardial injury is mediated through matrix metalloproteinase-2
aDepartment of Pharmacology, Cardiovascular Research Group, University of Alberta, 4-62 Heritage Medical Research Centre, Edmonton, Alberta, T6G 2S2 Canada
bDepartment of Pediatrics, Cardiovascular Research Group, University of Alberta, 4-62 Heritage Medical Research Centre, Edmonton, Alberta, T6G 2S2 Canada
* Corresponding author. Tel.: +1-780-492-6581; fax: +1-780-492-9753 richard.schulz{at}ualberta.ca
Objectives: Peroxynitrite (ONOO–) mediates in part both ischemia–reperfusion and pro-inflammatory cytokine-induced injury to the heart. As oxidants like ONOO– are known to activate matrix metalloproteinases (MMPs), we examined whether they play a role in the detrimental action of ONOO– in isolated perfused rat hearts. Methods: Hearts were isolated from Sprague–Dawley rats and perfused retrogradely with Krebs–Henseleit buffer under constant flow. Peroxynitrite (30 and 80 µM) was infused into the hearts for 15 min. The release of MMPs into the coronary effluent and level of MMPs in the myocardium were measured by gelatin zymography. Results: The main gelatinolytic activity in control effluent was 72-kDa corresponding to pro-MMP-2. Infusion of ONOO– (80 µM) for 15 min caused a vasodilatation which peaked at 5 min and then converted into vasoconstriction by 15 min. It also caused a rapid increase in the release of 72-kDa activity within 10 min and a progressive decline in cardiac mechanical function. In contrast, decomposed ONOO– caused no change in vascular tone, the release of 72-kDa activity or mechanical function. The MMPs inhibitor PD-166793 prevented the ONOO–-induced loss in myocardial mechanical function. Detoxification of ONOO– with glutathione prevented both the enhancement in coronary effluent 72-kDa activity and the decline in mechanical function. Conclusions: Acute cardiac toxicity induced by ONOO– is mediated by MMP-2.
KEYWORDS Contractile function; Heart failure; Nitric oxide
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. D. Kandasamy and R. Schulz Glycogen synthase kinase-3{beta} is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts Cardiovasc Res, September 1, 2009; 83(4): 698 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Kandasamy, A. K. Chow, M. A.M. Ali, and R. Schulz Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix Cardiovasc Res, August 20, 2009; (2009) cvp268v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kusmic, G. Lazzerini, F. Coceani, R. Barsacchi, A. L'Abbate, and G. Sambuceti Paradoxical coronary microcirculatory constriction during ischemia: a synergic function for nitric oxide and endothelin Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1814 - H1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Alfonso-Jaume, M. R. Bergman, R. Mahimkar, S. Cheng, Z. Q. Jin, J. S. Karliner, and D. H. Lovett Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1838 - H1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Manukhina, H. F. Downey, and R. T. Mallet Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia. Experimental Biology and Medicine, April 1, 2006; 231(4): 343 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Giricz, M. M. Lalu, C. Csonka, P. Bencsik, R. Schulz, and P. Ferdinandy Hyperlipidemia Attenuates the Infarct Size-Limiting Effect of Ischemic Preconditioning: Role of Matrix Metalloproteinase-2 Inhibition J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 154 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sawicki, H. Leon, J. Sawicka, M. Sariahmetoglu, C. J. Schulze, P. G. Scott, D. Szczesna-Cordary, and R. Schulz Degradation of Myosin Light Chain in Isolated Rat Hearts Subjected to Ischemia-Reperfusion Injury: A New Intracellular Target for Matrix Metalloproteinase-2 Circulation, July 26, 2005; 112(4): 544 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Lalu, E. Pasini, C. J. Schulze, M. Ferrari-Vivaldi, G. Ferrari-Vivaldi, T. Bachetti, and R. Schulz Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart Eur. Heart J., January 1, 2005; 26(1): 27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, S. J. Armstrong, I. A. Arenas, D. J. Pehowich, and S. T. Davidge Cardioprotection by chronic estrogen or superoxide dismutase mimetic treatment in the aged female rat Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H165 - H171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Berry and J. M. Hare Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications J. Physiol., March 15, 2004; 555(3): 589 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Huang, S. F. Vatner, A. P. Peppas, G. Yang, and R. K. Kudej Cardiac Nerves Affect Myocardial Stunning Through Reactive Oxygen and Nitric Oxide Mechanisms Circ. Res., October 31, 2003; 93(9): 866 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Qun Gao, G. Sawicki, W. L Suarez-Pinzon, T. Csont, M. Wozniak, P. Ferdinandy, and R. Schulz Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction Cardiovasc Res, February 1, 2003; 57(2): 426 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bianchi, H. Wakiyama, R. Faro, T. Khan, J. D. McCully, S. Levitsky, C. Szabo, and F. W. Sellke A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs Ann. Thorac. Surg., October 1, 2002; 74(4): 1201 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, C. J. Schulze, W. L. Suarez-Pinzon, J. R.B. Dyck, G. Sawicki, and R. Schulz Intracellular Action of Matrix Metalloproteinase-2 Accounts for Acute Myocardial Ischemia and Reperfusion Injury Circulation, September 17, 2002; 106(12): 1543 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. H. Khadour, D. Panas, P. Ferdinandy, C. Schulze, T. Csont, M. M. Lalu, S. M. Wildhirt, and R. Schulz Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1108 - H1115. [Abstract] [Full Text] [PDF]
|
|