Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-26T12:59:38.578Z Has data issue: false hasContentIssue false
  • English
  • Français

Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy

Published online by Cambridge University Press:  27 October 2010

Tain-Yen Hsia ,
Jeremy M. Ringewald ,
Robert E. Stroud ,
Nadia Roessler ,
Nidhi Kumar ,
Scott T. Reeves  and
Francis G. Spinale
Tain-Yen Hsia
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Jeremy M. Ringewald
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Robert E. Stroud
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Nadia Roessler
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Nidhi Kumar
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Scott T. Reeves
Affiliation:
Department of Anesthesia and Perioperative Medicine, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Francis G. Spinale*
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
*
Correspondence to: F. G. Spinale, MD, PhD, Cardiothoracic Surgery, Strom Thurmond Research Center, 114 Doughty Street, Suite 625, Charleston, South Carolina 29425, United States of America. Tel: (843) 876 5186; Fax: (843) 876 5187; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Dilated cardiomyopathy is an important cause of cardiac failure in both children and adults, but is more progressive in children. In adult dilated cardiomyopathy, left ventricular remodelling is associated with changes in the plasma levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases. Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase changes in paediatric dilated cardiomyopathy have not been examined. This study developed a low blood volume, high-sensitivity assay to test the hypothesis that unique and differential plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase profile exist in patients with paediatric dilated cardiomyopathy.

Methods/results

A systemic blood sample (1 millilitre) was obtained from seven children aged 8 plus or minus 7 years with dilated cardiomyopathy and 26 age-matched normal volunteers. Using a high-throughput multiplex suspension immunoassay, plasma levels were quantified for collagenases (matrix metalloproteinase-8), gelatinases (matrix metalloproteinase-2 and -9), lysins (matrix metalloproteinase-3 and -7), and tissue inhibitor of metalloproteinases-1, -2, and -4. The matrix metalloproteinase to tissue inhibitors of metalloproteinases ratios were also calculated. The plasma matrix metalloproteinase-2, -7, -8, and -9 levels were increased by greater than twofold in patients with dilated cardiomyopathy than normal patients (with p less than 0.05). Patients with dilated cardiomyopathy also had significantly higher tissue inhibitors of metalloproteinases-1 and -4 (298% and 230%; with p less than 0.05).

Conclusions

These unique findings show that a specific plasma matrix metalloproteinase/tissue inhibitor of metalloproteinase profile occurs in paediatric dilated cardiomyopathy when compared to the cases of normal children. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of dilated cardiomyopathy in children and may provide a novel biomarker platform in paediatric dilated cardiomyopathy.

Keywords

Cardiac failureremodellingplasmamyocardialbiomarker
Type
Original Articles
Information
Cardiology in the Young , Volume 21 , Issue 1 , February 2011 , pp. 52 - 61
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Towbin, JA, Lowe, AM, Colan, SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 2006; 296: 1867–1876.Google Scholar
2. Spinale, FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007; 87: 1285–1342.Google Scholar
3. Gunja-Smith, Z, Morales, AR, Romanelli, R, Woessner, JF Jr. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol 1996; 148: 1639–1648.Google ScholarPubMed
4. Spinale, FG. Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res 2002; 90: 520–530.Google Scholar
5. Spinale, FG, Coker, ML, Heung, LJ, et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation 2000; 102: 1944–1949.CrossRefGoogle ScholarPubMed
6. Ahmed, SH, Clark, LL, Pennington, WR, et al. Matrix metalloproteinases/tissue inhibitors of metalloproteinases: relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease. Circulation 2006; 113: 2089–2096.CrossRefGoogle ScholarPubMed
7. Wilson, EM, Gunasinghe, HR, Coker, ML, et al. Plasma matrix metalloproteinase and inhibitor profiles in patients with heart failure. J Card Fail 2002; 8: 390–398.Google Scholar
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: 484–487.CrossRefGoogle ScholarPubMed
9. Frantz, S, Stork, S, Michels, K, et al. Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: an independent predictor of mortality. Eur J Heart Fail 2008; 10: 388–395.Google Scholar
10. Gottschalk, PG, Dunn, JR. The five-parameter logistic: a characterization and comparison with the four-parameter logistic. Anal Biochem 2005; 343: 54–65.Google Scholar
11. Bigg, HF, Shi, YE, Liu, YE, Steffensen, B, Overall, CM. Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2. J Biol Chem 1997; 272: 15496–15500.Google Scholar
12. Greene, J, Wang, M, Liu, YE, Raymond, LA, Rosen, C, Shi, YE. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem 1996; 271: 30375–30380.Google Scholar
13. Cheung, C, Luo, H, Yanagawa, B, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in coxsackievirus-induced myocarditis. Cardiovasc Pathol 2006; 15: 63–74.Google Scholar
14. Li, YY, Feldman, AM, Sun, Y, McTiernan, CF. Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation 1998; 98: 1728–1734.Google Scholar
15. Yokoseki, O, Yazaki, Y, Suzuki, J, Imamura, H, Takenaka, H, Isobe, M. Association of matrix metalloproteinase expression and left ventricular function in idiopathic dilated cardiomyopathy. Jpn Circ J 2000; 64: 352–357.Google Scholar
16. Schwartzkopff, B, Fassbach, M, Pelzer, B, Brehm, M, Strauer, BE. Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy. Eur J Heart Fail 2002; 4: 439–444.CrossRefGoogle ScholarPubMed
17. Jordan, A, Roldan, V, Garcia, M, et al. Matrix metalloproteinase-1 and its inhibitor, TIMP-1, in systolic heart failure: relation to functional data and prognosis. J Intern Med 2007; 262: 385–392.Google Scholar
18. Kelly, D, Khan, SQ, Thompson, M, et al. Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction. Eur Heart J 2008; 29: 2116–2124.CrossRefGoogle ScholarPubMed
19. Yan, AT, Yan, RT, Spinale, FG, et al. Plasma matrix metalloproteinase-9 level is correlated with left ventricular volumes and ejection fraction in patients with heart failure. J Card Fail 2006; 12: 514–519.Google Scholar
20. Sundstrom, J, Evans, JC, Benjamin, EJ, et al. Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study. Circulation 2004; 109: 2850–2856.CrossRefGoogle ScholarPubMed
21. Lubos, E, Schnabel, R, Rupprecht, HJ, et al. Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study. Eur Heart J 2006; 27: 150–156.CrossRefGoogle ScholarPubMed
22. Sundstrom, J, Evans, JC, Benjamin, EJ, et al. Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study. Eur Heart J 2004; 25: 1509–1516.Google Scholar
23. Noji, Y, Shimizu, M, Ino, H, et al. Increased circulating matrix metalloproteinase-2 in patients with hypertrophic cardiomyopathy with systolic dysfunction. Circ J 2004; 68: 355–360.CrossRefGoogle ScholarPubMed
24. Overall, CM, Butler, GS. Protease yoga: extreme flexibility of a matrix metalloproteinase. Structure 2007; 15: 1159–1161.Google Scholar
25. Picard, F, Brehm, M, Fassbach, M, et al. Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP-1) and its inhibitor (TIMP-1) in DCM patients. Clin Res Cardiol 2006; 95: 261–269.CrossRefGoogle Scholar
26. Yarbrough, WM, Mukherjee, R, Brinsa, TA, et al. Matrix metalloproteinase inhibition modifies left ventricular remodeling following myocardial infarction. J Thorac Cardiovasc Surg 2003; 125: 602–610.Google Scholar
27. Visse, R, Nagase, H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92: 827–839.Google Scholar
28. Clark, IM, Swingler, TE, Sampieri, CL, Edwards, DR. The regulation of matrix metalloproteinases and their inhibitors. Int J Biochem Cell Biol 2008; 40: 1362–1378.Google Scholar
29. Cuenca, J, Martín-Sanz, P, Alvarez-Barrientos, AM, Boscá, L, Goren, N. Infiltration of inflammatory cells plays an important role in matrix metalloproteinase expression and activation in the heart during sepsis. Am J Pathol 2006; 169: 1567–1576.Google Scholar
30. Fitzsimmons, PJ, Forough, R, Lawrence, ME, et al. Urinary levels of matrix metalloproteinase 9 and 2 and tissue inhibitor of matrix metalloproteinase in patients with coronary artery disease. Atherosclerosis 2007; 194: 196–203.Google Scholar
31. Lauhio, A, Sorsa, T, Srinivas, R, et al. Urinary matrix metalloproteinase-8, -9, -14 and their regulators (TRY-1, TRY-2, TATI) in patients with diabetic nephropathy. Ann Med 2008; 40: 312–320.Google Scholar
32. Tziakas, DN, Chalikias, GK, Papaioakeim, M, et al. Comparison of levels of matrix metalloproteinase-2 and -3 in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy. Am J Cardiol 2005; 96: 1449–1451.CrossRefGoogle ScholarPubMed