Circulating Matrix Metalloproteinase 3 due to Myocardial Ischemia

Authors

  • Stavros Siminelakis
  • Angeliki Kotsanti
  • Nicholas Kolaitis
  • Dimitra Niokou
  • Ioanna Vlachou
  • George Dimakopoulos
  • Chrysanthy Papadopoulou

DOI:

https://doi.org/10.1532/HSF98.20081152

Abstract

Background: Experimental data suggest that matrix metalloproteinases (MMPs) such as MMP-3 have a central role in the remodeling period after a myocardial infarction (MI). The aim of this study was to use an experimental small-animal model to investigate the fluctuation in MMP-3 levels occurring in vivo after an acute MI.

Methods: We studied 13 New Zealand white rabbits weighing between 3 and 4 kg. After anesthetizing the animals, we performed a tracheotomy and induced an acute MI in 10 of the animals by occluding the left anterior descending coronary artery for 45 minutes. The remaining 3 rabbits constituted the control group. Three hours after reperfusion, blood samples were taken for biomedical analyses.

Results: Three hours after the artificially induced acute MI, serum MMP-3 levels were decreased by almost 50%. Cardiac troponin I (cTnI) concentrations were increased greatly (90-fold) after MI, further validating the efficiency of our experimental in vivo model of acute MI.

Conclusion: Combining the data, we demonstrated that acute MI caused an early reduction in MMP-3 levels. The range of MMP-3 reduction is limited compared with other factors predicting MI, such as cTnI, which increases its usefulness. We demonstrated, however, that plasma fluctuation in MMP-3 levels could be used as a supplementary independent predictor of cardiovascular events in patients with stable coronary artery disease. This acute MI model used in our controlled setting proved to be a reliable and safe method for conducting in vivo studies.

References

Abbott Laboratories. 1997. Abbott AXSYM System. Abbott Park, IL: Abbott Laboratories.nAbbott Laboratories. 2001. AxSYM System Operation Manual. Abbott Park, IL: Abbott Laboratories.nArdelt P, Dorka P, Jaquet K, et al. 1998. Microanalysis and distribution of cardiac troponin I phospho species in heart areas. Biol Chem 379:341-7.nBers DM. 2002. Cardiac Na/Ca exchange function in rabbit, mouse and man: What's the difference? J Mol Cell Cardiol 34:369-73.nBoyett MR, Jewell BR. 1978. A study of the factors responsible for rate-dependent shortening of the action potential in mammalian ventricular muscle. J Physiol 285:359-80.nCommittee on Care and Use of Laboratory Animals. 1996. Guide for the care and use of laboratory animals. US Dept. of Health and Human Services Publ. No. 85-23. Bethesda, MD: National Institutes of Health.nGreemers EE, Cleutjens JP, Smits JF, Daemen MJ. 2001. Matrix metalloproteinase inhibition after myocardial infarction: review. Circ Res 89:201-10.nIliodromitis EK, Kremastinos DT, Katritsis DG, Papadopoulos CC, Hearse DJ. 1997. Multiple cycles of preconditioning cause loss of protection in open-chest rabbits. J Mol Cell Cardiol 29:915-20.nLindsey ML, Gannon J, Aikawa M, et al. 2002. Selective matrix metalloproteinase inhibition reduces left ventricular remodeling but does not inhibit angiogenesis after myocardial infarction. Circulation 105:753-8.nLorell BH, Isoyama S, Grice WN, Weinberg EO, Apstein CS. 1988. Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood-perfused rabbit hearts. Circ Res 63:457-67.nLu L, Gunja-Smith Z, Woessner JF, et al. 2000. Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo. Am J Physiol Heart Circ Physiol 279:601-9.nMarian AJ, Wu Y, Lim DS, et al. 1999. A transgenic rabbit model for human hypertrophic cardiomyopathy. J Clin Invest 104:1683-92.nOgata Y, Enghild JJ, Nagase H. 1992. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581-4.nOkada Y, Takeuchi N, Tomita K, Nakanishi I, Nagase H. 1989. Immunolocalization of MMP-3 (stromelysin) in rheumatoid synovioblasts (B cells): correlation with rheumatoid arthritis. Ann Rheum Dis 48:645-53.nOkubo N, Hombrouck C, Fomes P, et al. 2000. Cardiac troponin I and myocardial contusion in the rabbit. Anesthesiology 93:811-7.nRomanic AM, Burns-Kurtis CL, Gout B, Berrebi-Bertrand I, Ohlstein EH. 2001. Matrix metalloproteinase expression in cardiac myocytes following myocardial infarction in the rabbit. Life Sci 68:799-814.nSamnegard A, Silveria A, Tornvall P, Hamsten A, Ericsson CG, Eriksson P. 2006. Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction. J Intern Med 259:530-6.nSanbe A, James J, Tuzcu V, et al. 2005. Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy. Circulation 111:2330-8.nSpinale FG. 2002. Matrix metalloproteinases: regulation and dysregulation in the failing heart [review]. Circ Res 90:520-30.nWu TC, Leu HB, Lin WT, Lin CP, Lin SJ, Chen JW. 2005. Plasma MMP-3 level is an independent prognostic factor in stable coronary artery disease. Eur J Clin Invest 35:537-45.nYellon DM, Iliodromitis E, Latchman DS, et al. 1992. Whole body stress fails to limit infarct size in the reperfused rabbit heart. Cardiovasc Res 26:342-6.n

Published

2009-08-14

How to Cite

Siminelakis, S., Kotsanti, A., Kolaitis, N., Niokou, D., Vlachou, I., Dimakopoulos, G., & Papadopoulou, C. (2009). Circulating Matrix Metalloproteinase 3 due to Myocardial Ischemia. The Heart Surgery Forum, 12(4), E230-E234. https://doi.org/10.1532/HSF98.20081152

Issue

Section

Article