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Matrix Metalloproteinase 9 (MMP-9)

The Middle-Man of Post-myocardial Infarction Extracellular Matrix Remodeling

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Book cover Cardiac Fibrosis and Heart Failure: Cause or Effect?

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 13))

Abstract

The substantial involvement of matrix metalloproteinase-9 (MMP-9) in adverse cardiac extracellular matrix (ECM) remodeling makes it one of the most widely investigated MMPs. MMP-9 functions primarily by directly degrading and activating ECM structural and non-structural molecules to regulate cardiac tissue remodeling. This activity is opposed under physiological conditions by a set of endogenous inhibitors known as tissue inhibitors of metalloproteinases (TIMPS). Following myocardial infarction (MI), this constraint is diminished and MMP-9 tissue and plasma levels acutely increase concomitant with a decline in cardiac function. MMP-9 loss-of-function experiments in multiple animal models of MI demonstrate an overall beneficial effect and emphasize the importance of MMP-9 inhibition as a therapeutic intervention. This chapter summarizes MMP-9 structure, transcriptional regulation, post-translational modification, and downstream ECM substrates. We also explore the overall important role of MMP-9 in adverse cardiac remodeling post-MI and its potential utility as a pathophysiological biomarker. Finally, we highlight MMP-9 endogenous and pharmacological inhibitors and the challenges that must be overcome to achieve clinical translation. This is a comprehensive review of MMP-9, from its biochemical structure to its potential role in clinical trials, and can serve as an introduction to young researchers who just joined this research area.

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Acknowledgements

We acknowledge support from National Institutes of Health (NIH) for T32HL105324, HL101430, HL075360, HL051971, GM104357, and HHSN 268201000036C (N01-HV-00244) for the San Antonio Cardiovascular Proteomics Center, and from the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505.

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Authors and Affiliations

  1. San Antonio Cardiovascular Proteomics Center, San Antonio, USA

    Fouad A. Zouein, Ashley DeCoux, Yuan Tian, Yu-Fang Jin & Merry L. Lindsey

  2. Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    Fouad A. Zouein, Ashley DeCoux, Yuan Tian, Jared A. White & Merry L. Lindsey

  3. Department of Electrical and Computer Engineering, The University of Texas at San Antonio, San Antonio, TX, USA

    Yu-Fang Jin

  4. Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA

    Merry L. Lindsey

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  1. Fouad A. Zouein
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  2. Ashley DeCoux
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  3. Yuan Tian
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  4. Jared A. White
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  5. Yu-Fang Jin
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Correspondence to Merry L. Lindsey .

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  1. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada

    Ian M.C. Dixon

  2. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

    Jeffrey T. Wigle

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Zouein, F., DeCoux, A., Tian, Y., White, J., Jin, YF., Lindsey, M. (2015). Matrix Metalloproteinase 9 (MMP-9). In: Dixon, I., Wigle, J. (eds) Cardiac Fibrosis and Heart Failure: Cause or Effect?. Advances in Biochemistry in Health and Disease, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-17437-2_13

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