Circulation. 2002;106:1543-1549
Published online before print August 26, 2002, doi: 10.1161/01.CIR.0000028818.33488.7B
Published online before print August 26, 2002, doi: 10.1161/01.CIR.0000028818.33488.7B
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:1543.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Intracellular Action of Matrix Metalloproteinase-2 Accounts for Acute Myocardial Ischemia and Reperfusion Injury
From the Departments of Pharmacology (W.W., C.J.S., G.S., R.S.), Pediatrics (J.R.B.D., R.S.), and Medicine (W.L.S.-P.), University of Alberta, Edmonton, Alberta, Canada.
Correspondence to Dr Richard Schulz, Departments of Pediatrics and Pharmacology, 4-62 Heritage Medical Research Center, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. E-mail richard.schulz{at}ualberta.ca
Background— Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the proteolytic degradation of the thin filament protein troponin I; however, the protease responsible for this remains obscure.
Methods and Results— Here we report that matrix metalloproteinase-2 is colocalized with troponin I within the thin myofilaments of cardiomyocytes in ischemic-reperfused hearts and that troponin I is a novel intracellular target for proteolytic cleavage by matrix metalloproteinase-2. Inhibition of matrix metalloproteinase-2 activity prevented ischemia-reperfusion-induced troponin I degradation and improved the recovery of mechanical function of the heart.
Conclusions— These data reveal for the first time a novel molecular mechanism by which matrix metalloproteinase-2 causes acute myocardial dysfunction after ischemia-reperfusion-injury and that matrix metalloproteinase-2 has a biological action within the cell.
Key Words: metalloproteinases • ischemia • reperfusion • troponin
This article has been cited by other articles:
 |
|
 |
|
  Y. Matsumoto, I.-K. Park, and K. Kohyama Matrix Metalloproteinase (MMP)-9, but Not MMP-2, Is Involved in the Development and Progression of C Protein-Induced Myocarditis and Subsequent Dilated Cardiomyopathy J. Immunol., October 1, 2009; 183(7): 4773 - 4781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 J. Sundstrom, E. Ingelsson, L. Berglund, B. Zethelius, L. Lind, P. Venge, and J. Arnlov Cardiac troponin-I and risk of heart failure: a community-based cohort study Eur. Heart J., April 1, 2009; 30(7): 773 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Kelley, D. Siegel, D. M. Fedor, Y. Adkins, and B. E. Mackey DHA Supplementation Decreases Serum C-Reactive Protein and Other Markers of Inflammation in Hypertriglyceridemic Men J. Nutr., March 1, 2009; 139(3): 495 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Moshal, M. Kumar, N. Tyagi, P. K. Mishra, N. Metreveli, W. E. Rodriguez, and S. C. Tyagi Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion of NMDA-R1 Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H887 - H892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Romero-Perez, E. Fricovsky, K. G. Yamasaki, M. Griffin, M. Barraza-Hidalgo, W. Dillmann, and F. Villarreal Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection J. Am. Coll. Cardiol., September 23, 2008; 52(13): 1086 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Moshal, S. M. Tipparaju, T. P. Vacek, M. Kumar, M. Singh, I. E. Frank, P. K. Patibandla, N. Tyagi, J. Rai, N. Metreveli, et al. Mitochondrial matrix metalloproteinase activation decreases myocyte contractility in hyperhomocysteinemia Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H890 - H897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Adya, B. K. Tan, A. Punn, J. Chen, and H. S. Randeva Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis Cardiovasc Res, May 1, 2008; 78(2): 356 - 365. [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]
|
|
|
|
 |
|
 M. Sariahmetoglu, B. D. Crawford, H. Leon, J. Sawicka, L. Li, B. J. Ballermann, C. Holmes, L. G. Berthiaume, A. Holt, G. Sawicki, et al. Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation FASEB J, August 1, 2007; 21(10): 2486 - 2495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aupperle, J. Garbade, A. Schubert, M. Barten, S. Dhein, H.-A Schoon, and F.-W Mohr Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model Vet. Pathol., July 1, 2007; 44(4): 494 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Bergman, J. R. Teerlink, R. Mahimkar, L. Li, B.-Q. Zhu, A. Nguyen, S. Dahi, J. S. Karliner, and D. H. Lovett Cardiac matrix metalloproteinase-2 expression independently induces marked ventricular remodeling and systolic dysfunction Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1847 - H1860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Paisley, C. J. O'Callaghan, K. C. Lewandowski, C. Parkinson, M. E. Roberts, W. M. Drake, J. P. Monson, P. J. Trainer, and H. S. Randeva Reductions of Circulating Matrix Metalloproteinase 2 and Vascular Endothelial Growth Factor Levels after Treatment with Pegvisomant in Subjects with Acromegaly J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4635 - 4640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mukherjee, J. T. Mingoia, J. A. Bruce, J. S. Austin, R. E. Stroud, G. P. Escobar, D. M. McClister Jr, C. M. Allen, M. A. Alfonso-Jaume, M. E. Fini, et al. Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2216 - H2228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Hockenbery MMPs in Unusual Places Am. J. Pathol., October 1, 2006; 169(4): 1101 - 1103. [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]
|
|
|
|
|
|
K. C. Lewandowski, J. Komorowski, D. P. Mikhalidis, M. Bienkiewicz, B. K. Tan, C. J. O'Callaghan, A. Lewinski, G. Prelevic, and H. S. Randeva Effects of Hormone Replacement Therapy Type and Route of Administration on Plasma Matrix Metalloproteinases and Their Tissue Inhibitors in Postmenopausal Women J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3123 - 3130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Viappiani and R. Schulz Detection of specific nitrotyrosine-modified proteins as a marker of oxidative stress in cardiovascular disease Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2167 - H2168. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Macotela, M. B. Aguilar, J. Guzman-Morales, J. C. Rivera, C. Zermeno, F. Lopez-Barrera, G. Nava, C. Lavalle, G. M. de la Escalera, and C. Clapp Matrix metalloproteases from chondrocytes generate an antiangiogenic 16 kDa prolactin J. Cell Sci., May 1, 2006; 119(9): 1790 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Lewandowski, J. Komorowski, C. J. O'Callaghan, B. K. Tan, J. Chen, G. M. Prelevic, and H. S. Randeva Increased Circulating Levels of Matrix Metalloproteinase-2 and -9 in Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1173 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nagase, R. Visse, and G. Murphy Structure and function of matrix metalloproteinases and TIMPs Cardiovasc Res, February 15, 2006; 69(3): 562 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Y. Wang, M. R. Bergman, A. P. Nguyen, S. Turcato, P. M. Swigart, M. C. Rodrigo, P. C. Simpson, J. S. Karliner, D. H. Lovett, and A. J. Baker Cardiac transgenic matrix metalloproteinase-2 expression directly induces impaired contractility Cardiovasc Res, February 15, 2006; 69(3): 688 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pardo and M. Selman Matrix metalloproteases in aberrant fibrotic tissue remodeling. Proceedings of the ATS, January 1, 2006; 3(4): 383 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsusaka, M. Ikeuchi, S. Matsushima, T. Ide, T. Kubota, A. M. Feldman, A. Takeshita, K. Sunagawa, and H. Tsutsui Selective disruption of MMP-2 gene exacerbates myocardial inflammation and dysfunction in mice with cytokine-induced cardiomyopathy Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1858 - H1864. [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]
|
|
|
|
|
|
J. Chen, C.-H. Tung, J. R. Allport, S. Chen, R. Weissleder, and P. L. Huang Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction Circulation, April 12, 2005; 111(14): 1800 - 1805. [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]
|
|
|
|
 |
|
 R. da Silva, E. Lucchinetti, T. Pasch, M. C. Schaub, and M. Zaugg Ischemic but not pharmacological preconditioning elicits a gene expression profile similar to unprotected myocardium Physiol Genomics, December 15, 2004; 20(1): 117 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Konstantinov, S. Arab, R. K. Kharbanda, J. Li, M. M. H. Cheung, V. Cherepanov, G. P. Downey, P. P. Liu, E. Cukerman, J. G. Coles, et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans Physiol Genomics, September 16, 2004; 19(1): 143 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaikita, T. Hayasaki, T. Okuma, W. A. Kuziel, H. Ogawa, and M. Takeya Targeted Deletion of CC Chemokine Receptor 2 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction Am. J. Pathol., August 1, 2004; 165(2): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Randeva, K. C. Lewandowski, J. Komorowski, R. D. Murray, C. J. O'Callaghan, E. W. Hillhouse, H. Stepien, and S. M. Shalet Growth Hormone Replacement Decreases Plasma Levels of Matrix Metalloproteinases (2 and 9) and Vascular Endothelial Growth Factor in Growth Hormone-Deficient Individuals Circulation, May 25, 2004; 109(20): 2405 - 2410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Soergel, D. Georgakopoulos, L. B. Stull, D. A. Kass, and A. M. Murphy Augmented systolic response to the calcium sensitizer EMD-57033 in a transgenic model with troponin I truncation Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1785 - H1792. [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]
|
|
|
|
|
|
F. J. Villarreal, M. Griffin, J. Omens, W. Dillmann, J. Nguyen, and J. Covell Early Short-Term Treatment With Doxycycline Modulates Postinfarction Left Ventricular Remodeling Circulation, September 23, 2003; 108(12): 1487 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Schulze, W. Wang, W. L. Suarez-Pinzon, J. Sawicka, G. Sawicki, and R. Schulz Imbalance Between Tissue Inhibitor of Metalloproteinase-4 and Matrix Metalloproteinases During Acute Myoctardial Ischemia-Reperfusion Injury Circulation, May 20, 2003; 107(19): 2487 - 2492. [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]
|
|