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The impact of aging on cardiac extracellular matrix

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Abstract

Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and the gradual development of cardiac fibrosis are hallmarks of cardiac aging. In the absence of a secondary insult such as hypertension, these changes are subtle and result in slight to moderate impaired myocardial function, particularly diastolic function. While collagen deposition and cross-linking increase during aging, extracellular matrix (ECM) degradation capacity also increases due to increased expression of matrix metalloproteinases (MMPs). Of the MMPs elevated with cardiac aging, MMP-9 has been extensively evaluated and its roles are reviewed here. In addition to proteolytic activity on ECM components, MMPs oversee cell signaling during the aging process by modulating cytokine, chemokine, growth factor, hormone, and angiogenic factor expression and activity. In association with elevated MMP-9, macrophage numbers increase in an age-dependent manner to regulate the ECM and angiogenic responses. Understanding the complexity of the molecular interactions between MMPs and the ECM in the context of aging may provide novel diagnostic indicators for the early detection of age-related fibrosis and cardiac dysfunction.

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Acknowledgements

This work was supported by the National Institute of Health HL075360, HL129823, HL051971, T32HL105324, GM114833, and GM104357 and by the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505.

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  1. Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Room G351-04, Jackson, MS, USA

    Cesar A. Meschiari, Osasere Kelvin Ero & Merry L. Lindsey

  2. Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA

    Haihui Pan & Toren Finkel

  3. G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, 39216-4505, USA

    Merry L. Lindsey

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  1. Cesar A. Meschiari
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  2. Osasere Kelvin Ero
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Correspondence to Merry L. Lindsey.

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Meschiari, C., Ero, O.K., Pan, H. et al. The impact of aging on cardiac extracellular matrix. GeroScience 39, 7–18 (2017). https://doi.org/10.1007/s11357-017-9959-9

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