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

  • Merry L. Lindsey
  • Lisandra E. de Castro Brás
Chapter
Part of the Molecular and Translational Medicine book series (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.

Keywords

Matrix metalloproteinase Aging Extracellular matrix Inflammation Macrophage Myocyte MMP-9 

Notes

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Merry L. Lindsey
    • 1
    • 2
  • Lisandra E. de Castro Brás
    • 3
  1. 1.Mississippi Center for Heart Research, Department of Physiology and BiophysicsUniversity of Mississippi Medical CenterJacksonUSA
  2. 2.Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical CenterJacksonUSA
  3. 3.Department of Physiology, Brody School of MedicineEast Carolina UniversityGreenvilleUSA

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