Medical University of Sofia, Sofia, Bulgaria
*Corresponding author: Katerina D. Vitlianova, MD, PhD, Senior assistant professor, Dept. of Internal Medicine «dr.St. Kirkovich», Clinic of Cardiology, Medical University of Sofia, University Hospital «Alexandrovska», 1 St Georgi Sofiiski str., 1431 Sofia, Bulgaria. E-mail: k. vitlianova@abv.bg
Matrix metalloproteinases (MMPs), particularly MMP-9, are estimated to play an important role in the progression of systolic chronic heart failure (CHF); however, the existing data is incomplete and controversial.
Purpose: The aim of this study was to investigate the changes in plasma MMP-9, associated with CHF and to determine the prognostic value of certain clinical parameters on MMP-9 levels.
Methods: Plasma MMP-9 was measured in 20 normal elderly controls (NEC) and in 59 patients with CHF. Systolic dysfunction was defined as left ventricular ejection fraction (LVEF) ≤40%. Plasma MMP-9 levels and brain natriuretic peptide (BNP) were measured performing immunoassays. Normally distributed variables were reported with mean and skewed variables with the median. Group comparisons were made with the independent t-test, Mann-Whitney U-test and χ2-test, where appropriate. Univariate associations of the variables with MMP-9 were investigated using linear regression analyses. Natural logarithmic transformation was used for skewed variables, including MMP-9 and BNP. Multiple linear regression was used to investigate the independent relations to MMP-9. Statistical analyses were conducted on the SPSS version 13.0 (SPSS Inc, Chicago, IL).
Results: Plasma MMP-9 concentrations (ng/ml) were significantly higher in HF patients (median 1.7, range 0.5-7.3), compared with NEC (median 1.2, range 0.6-2.9) (p=0.01). Circulating BNP and functional class were not significantly correlated with plasma MMP-9. In addition, no significant relationships were observed between MMP-9 and etiology, leucocytes, and creatinkinase (CK). Plasma levels of MMP-9 showed significant correlation with the clinical parameters LVEF, systolic blood pressure (SBP) and atrial fibrillation (AF). Independent predictive effect on MMP-9 levels in multiple regression analysis (F=7.7, p<0.01) were explored for AF, LVEF, SBP and COPD.
Conclusions: Plasma MMP-9 was observed to increase in subjects with CHF. Expectedly, MMP-9 was independently correlated with the degree of cardiac dysfunction and clinical parameters depending on it, including SBP and AF, and with the presence of COPD. Further studies are warranted on the concrete mechanisms of MMP-9 variations in patients with CHF.
1. Spinale FG. Matrix metalloproteinases. Regulation and dysregulation in the failing heart. Circ Res 2002; 90: 520-530.
2. Thomas CV, Coker ML, Zellner JL, Handy JR, Crumbley AJ, Spinale FG. Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation 1998; 97: 1708-1715.
3. Banfi C, Cavalca V, Veglia F, et al. Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure. Eur Heart J 2005; 26: 481-488.
4. Spinale FG, Coker ML, Krombach SR, et al. Matrix metalloproteinase inhibition during the development of congestive heart failure: effects on left ventricular dimensions and function. Circ Res 1999; 85: 364-376.
5. Mukherjee R, Widener C, Brinsa T, Dowdy KB, Scott AA, Sample J, Hendrick J, Escobar G, Joffs C, Lucas D, Zile M, Spinale F. Myocardial infarct expansion and matrix metalloproteinase inhibition. Circulation 2003; 107: 618–625.
6. Sundstrom J, Evans JC, Benjamin EJ, Levy D, Larson MG, Sawyer DB, Siwik DA, Colucci WS, Sutherland P, Wilson PWF, Vasan RS. Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures. Circulation 2004; 109: 2850–2856.
7. Frantz S, Störk S, K. Michels, M. Eigenthaler,G. Ertl, J. Bauersachs, C. E. Angermann. Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: An independent predictor of mortality. Eur J Heart Fail 2008; 10 (4):388-3958.
8. George J, Patal S, Wexler D, Roth A, Sheps D, Keren G. Circulating matrix metalloproteinase-2 but not matrix metalloproteinase-3, matrix metalloproteinase-9, or tissue inhibitor of metalloproteinase-1 predicts outcome in patients with congestive heart failure. Am Heart J 2005; 150 (3):484-7.
9. Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, Meyer J, Cambien F, Tiret L. AtheroGene Investigators. Plasma concentrations and genetic variation of matrix metalloproteinase-9 and prognosis of patients with cardiovascular disease. Circulation 2003; 109: 1579–1585.
10. Sackner-Bernstein JD. The myocardial matrix and the development and progression of ventricular remodeling. Curr Cardiol Rep 2000; 2:112–119.
11. Letsas KP, Filippatos GS, Pappas LK, Mihas CC, Markou V, Alexanian IP, et al. Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction. Clin Res Cardiol 2009; 98 (2): 101-6.
12. Nakano Y, Niida S, Dote K, Takenaka S, Hirao H, Miura F, Mari Ishida M, Shingu T, Sueda T, Yoshizumi M and Chayama K. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation. J Am Coll Cardiol 2004; 43:818-825.
13. Xu J, Guanggen Cui, Esmailian F, Plunkett M, Marelli D, Ardehali A, Odim J, Laks H, Sen L. Atrial Extracellular Matrix Remodeling and the Maintenance of Atrial Fibrillation Circulation 2004; 109:363-368
14. Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994; 330:1431–1438.
15. Yasmin, SW, McEniery CM, Dakham Z, Pusalkar P, Kaisa Maki-Petaja, Ashby MJ, Cockcroft JR, Wilkinson IB. Matrix Metalloproteinase-9 (MMP-9), MMP-2, and Serum Elastase Activity Are Associated With Systolic Hypertension and Arterial Stiffness. Arteriosclerosis, Thrombosis, and Vascular Biology 2005; 25:372-378
16. Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002; 110:625–632.
17. Medley TL, Cole TJ, Dart AM, Gatzka CD, Kingwell BA. Matrix metalloproteinase-9 influences large artery stiffness through effects on aortic gene and protein expression. Arterioscler Thromb Vasc Biol 2004; 24:1–6.
18. Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, Arveiler D, Luc G, Cambien F, Hamsten A, Watkins H, Henney AM. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 1999; 99:1788–1794.
Int J Biomed. 2011; 1(3):143-149. © 2011 International Medical Research and Development Corporation. All rights reserved.
