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Matrix Metalloproteinase-9-Dependent Mechanisms of Reduced Contractility and Increased Stiffness in the Aging Heart

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Fibrosis in Disease

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

With age, the myocardium gradually undergoes a resetting of homeostasis that includes structural and physiological adaptations. Cardiomyocyte hypertrophy is an initiating factor and, combined with a decoupling of angiogenesis, ultimately leads to a reduction in myocyte vessel number that drives an inflammatory response and extracellular matrix (ECM) accumulation. In the absence of a secondary injury, the changes associated with aging in the heart are subtle and result in slight to moderate impaired diastolic physiology. Collagen accumulates due to increased deposition and cross-linking; at the same time, the rate of ECM degradation also increases, due to increased expression of matrix metalloproteinases (MMPs). One MMP in particular, MMP-9, has a direct cause-and-effect relationship. MMP-9 proteolyzes a wide array of substrates, including ECM components, inflammatory components (cytokines, chemokines, and their receptors), and repair components (growth factors and angiogenic factors). Increased MMP-9 is linked to an increase in the number of macrophages. The connection between myocytes, perfusion, inflammation, and ECM accumulation and how MMP-9 regulates these processes are summarized here.

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Acknowledgments

This work was supported by the American Heart Association 14SDG18860050; the National Institute of Health HL075360, HL129823, HL051971, GM114833, GM115428, and GM104357; and 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. Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    Merry L. Lindsey

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

    Merry L. Lindsey

  3. Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    Lisandra E. de Castro Brás

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  1. Merry L. Lindsey
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Correspondence to Merry L. Lindsey .

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Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, Indiana Center for Musculoskeletal Health, Indianapolis, IN, USA

    Monte S. Willis

  2. Department of Health Promotion and Development, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA

    Cecelia C. Yates

  3. Department of Pharmacology and Department of Pathology and Lab Medicine, McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Jonathan C. Schisler

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Lindsey, M.L., de Castro Brás, L.E. (2019). Matrix Metalloproteinase-9-Dependent Mechanisms of Reduced Contractility and Increased Stiffness in the Aging Heart. In: Willis, M., Yates, C., Schisler, J. (eds) Fibrosis in Disease . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98143-7_12

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