American Heart Journal
Volume 152, Issue 1 , Page e9, July 2006

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in congestive heart failure

Department of Morphology, Estomatology, and Physiology, Dental School of Ribeirao Preto, University of São Paulo, Ribeirao Preto, São Paulo, Brazil

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, São Paulo, Brazil

Article Outline

 

Dear Editor:

George et al recently studied the prognostic value of circulating concentrations of some matrix metalloproteinases (MMPs) and of tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with congestive heart failure. They found that MMP-2, but not MMP-3, MMP-9, and TIMP-1, serum levels are a biomarker predicting mortality in patients with congestive heart failure.1 However, there is strong evidence showing that MMP-9 and TIMP-1 measurements in serum samples do not reflect the real circulating levels of these biomarkers. Measurements of MMP-9 and TIMP-1 levels in serum samples are artificially altered when compared with those measured in plasma samples.2, 3, 4, 5 In addition, no correlation was found between MMP-9 levels in serum and those in plasma samples.5 In this regard, we are very concerned with the number of articles of studies having mistakenly used serum instead of plasma to assess MMP-9 and TIMP levels in many different clinical conditions being published.6, 7 This technical issue may lead to unreliable conclusions. The probable biologic explanation for these extremely important differences in serum and plasma is that variable release of these markers by platelets or leukocytes occurs during platelet activation or the sampling process.2, 3 In summary, preanalytical conditions and other methodological issues are of major importance when assessing MMPs/TIMPs in clinical samples.8 Therefore, there is strong evidence indicating that serum samples should not be used to measure circulating MMP-9 levels as a diagnostic or prognostic marker of disease.

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References 

  1. George J, Patal S, Wexler D, et al. 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
  2. Jung K, Lein M, Laube C, et al. Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood. Clin Chim Acta. 2001;314:241–244
  3. Jung K, Laube C, Lein M, et al. Kind of sample as preanalytical determinant of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 2 in blood. Clin Chem. 1998;44:1060–1062
  4. Makowski GS, Ramsby ML. Use of citrate to minimize neutrophil matrix metalloproteinase-9 in human plasma. Anal Biochem. 2003;322:283–286
  5. Gerlach RF, Uzuelli JA, Souza-Tarla CD, et al. Effect of anticoagulants on plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Anal Biochem. 2005;344:147–149
  6. Tanus-Santos JE, Gerlach RF. Circulating matrix metalloproteinase-9 levels as a possible marker of aortic stiffness. Arterioscler Thromb Vasc Biol. 2005;25:e27
  7. Tanus-Santos JE, Gerlach RF. Serum samples should not be used to assess circulating matrix metalloproteinase-9 levels as a prognostic marker of disease. Int J Cancer. 2006;118:789
  8. Souza-Tarla CD, Uzuelli JA, Machado AA, et al. Methodological issues affecting the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Clin Biochem. 2005;38:410–414

PII: S0002-8703(06)00392-9

doi:10.1016/j.ahj.2006.04.022

American Heart Journal
Volume 152, Issue 1 , Page e9, July 2006

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