Chapter Seven - Matrix Metalloproteinases in Biologic Samples

https://doi.org/10.1016/B978-0-12-800141-7.00007-3Get rights and content

Abstract

Matrix metalloproteinases (MMPs) are an important class of endopeptidases, having a role in a diverse range of physiological and pathological processes. This chapter provides an overview of the key regulatory processes in MMP production and activation. The common techniques used to assess MMP activity are discussed and their various strengths and weaknesses presented. This comparison of methodologies is specifically intended to aid any investigator who wishes to determine the most appropriate analytical method for their future studies because any investigation of MMPs in biological samples should be cognizant of the key mechanisms influencing the expression and activity of these proteinases. The endogenous, preanalytic and analytic chemistry of MMP activation influences the interpretation of the various techniques widely employed throughout the literature. Therefore, the ability to accurately evaluate the true endogenous activity of MMPs is heavily dependent on a clear understanding of these processes.

Section snippets

Regulation of MMPs

In any experiment analyzing MMPs within biological specimens, it is important to understand the key mechanisms influencing the expression and activity of these proteinases. Because of their potentially potent physiological and pathogenic functions, MMPs are tightly regulated at the transcriptional, posttranscriptional, and posttranslational levels. In addition, protein activity is influenced by activators, inhibitors, and specific tissue-binding characteristics.

Detection of MMPs in Biological Samples, Total Zymogen Versus Enzymatic Activity

When considering the assessment of MMPs within a biological sample, it is important to consider which aspect of MMP expression (total zymogen, prodomain cleaved, TIMP-bound, or endogenously active) is most biologically relevant to the research question being investigated. This is an important determinant, as direct measurement of MMP protein will not distinguish active from inactive enzyme. At this point, it is probably worth clarifying some of the terminology used regarding the various

Confounders of MMP Measurements

A number of variables have been implicated as confounders of circulating MMP levels, including age [64], gender, white cell count [65], and certain medications [66], [67], [68]. Altered MMP expression has also been implicated in a wide range of pathophysiological conditions including obesity [69], cancer [70], [71], liver fibrosis [72], rheumatoid arthritis [73], heart disease [65], [74], [75], [76], and peripheral vascular disease [77].

Controversy exists regarding several preanalytical aspects

References (89)

  • M.W. Olson et al.

    Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2

    J. Biol. Chem.

    (1997)
  • S. Higashi et al.

    Identification of a region of beta-amyloid precursor protein essential for its gelatinase A inhibitory activity

    J. Biol. Chem.

    (2003)
  • J.D. Mott et al.

    Post-translational proteolytic processing of procollagen C-terminal proteinase enhancer releases a metalloproteinase inhibitor

    J. Biol. Chem.

    (2000)
  • J. Oh et al.

    The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis

    Cell

    (2001)
  • D.E. Kleiner et al.

    Quantitative zymography: detection of picogram quantities of gelatinases

    Anal. Biochem.

    (1994)
  • M. Gawlak et al.

    High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses

    Neuroscience

    (2009)
  • C.R. Ban et al.

    Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction

    Diabetes Res. Clin. Pract.

    (2010)
  • E.M. Wilson et al.

    Plasma matrix metalloproteinase and inhibitor profiles in patients with heart failure

    J. Card. Fail.

    (2002)
  • G.P. Tarr et al.

    Pro-MMP-9/TIMP-1 ratio correlates poorly with a direct assessment of MMP-9 activity

    Clin. Biochem.

    (2011)
  • G.T. Jones et al.

    Active matrix metalloproteinases 3 and 9 are independently associated with coronary artery in-stent restenosis

    Atherosclerosis

    (2009)
  • J.W. Chu et al.

    Plasma active matrix metalloproteinase 9 associated to diastolic dysfunction in patients with coronary artery disease

    Int. J. Cardiol.

    (2011)
  • D.D. Bonnema et al.

    Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs)

    J. Card. Fail.

    (2007)
  • M.H. Tayebjee et al.

    Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease

    Am. J. Cardiol.

    (2005)
  • J. Evans et al.

    Simvastatin attenuates the activity of matrix metalloprotease-9 in aneurysmal aortic tissue

    Eur. J. Vasc. Endovasc. Surg.

    (2007)
  • K.H. Boeker et al.

    Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C

    Clin. Chim. Acta

    (2002)
  • B.L. Gruber et al.

    Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker

    Clin. Immunol. Immunopathol.

    (1996)
  • M.J. Hobeika et al.

    Matrix metalloproteinases in peripheral vascular disease

    J. Vasc. Surg.

    (2007)
  • D. Rouy et al.

    Plasma storage at − 80 degrees C does not protect matrix metalloproteinase-9 from degradation

    Anal. Biochem.

    (2005)
  • G.P. Tarr et al.

    Seasonal variation and stability of matrix metalloproteinase-9 activity and tissue inhibitor of matrix metalloproteinase-1 with storage at − 80 degrees C

    Clin. Biochem.

    (2011)
  • F. Mannello et al.

    Differences in both matrix metalloproteinase 9 concentration and zymographic profile between plasma and serum with clot activators are due to the presence of amorphous silica or silicate salts in blood collection devices

    Anal. Biochem.

    (2008)
  • G.S. Makowski et al.

    Use of citrate to minimize neutrophil matrix metalloproteinase-9 in human plasma

    Anal. Biochem.

    (2003)
  • F. Mannello et al.

    Heparin affects matrix metalloproteinases and tissue inhibitors of metalloproteinases circulating in peripheral blood

    Clin. Biochem.

    (2008)
  • R.F. Gerlach et al.

    Effect of anticoagulants on the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities

    Anal. Biochem.

    (2005)
  • C.D. Souza-Tarla et al.

    Methodological issues affecting the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities

    Clin. Biochem.

    (2005)
  • H. Nagase et al.

    Structure and function of matrix metalloproteinases and TIMPs

    Cardiovasc. Res.

    (2006)
  • S. Rivera et al.

    Metzincin proteases and their inhibitors: foes or friends in nervous system physiology?

    J. Neurosci.

    (2010)
  • F.X. Gomis-Ruth

    Structural aspects of the metzincin clan of metalloendopeptidases

    Mol. Biotechnol.

    (2003)
  • I. Massova et al.

    Matrix metalloproteinases: structures, evolution, and diversification

    FASEB J.

    (1998)
  • M.D. Sternlicht et al.

    How matrix metalloproteinases regulate cell behavior

    Annu. Rev. Cell Dev. Biol.

    (2001)
  • C. Yan et al.

    Regulation of matrix metalloproteinase gene expression

    J. Cell. Physiol.

    (2007)
  • Z.S. Galis et al.

    Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly

    Circ. Res.

    (2002)
  • U. Ikeda et al.

    Matrix metalloproteinases and coronary artery diseases

    Clin. Cardiol.

    (2003)
  • N.R. Keller et al.

    Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by interleukin-1alpha in human endometrial stromal cells

    J. Clin. Endocrinol. Metab.

    (2000)
  • Y. Zhang et al.

    Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha, granulocyte-macrophage CSF, and IL-1 beta through prostaglandin-dependent and -independent mechanisms

    J. Immunol.

    (1998)
  • Cited by (0)

    View full text