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Aging and Heart Failure pp 361–375Cite as

Aging-Associated Alterations in Myocardial Inflammation and Fibrosis: Pathophysiological Perspectives and Clinical Implications

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Abstract

Senescent hearts exhibit structural and molecular changes that result in impaired function and are associated with diminished ability to meet increased demand. Both animal model studies and clinical investigations suggest that fibrosis is a hallmark of cardiac aging. Expansion of the cardiac interstitium and accumulation of collagen in the aging heart cause a progressive increase in ventricular stiffness, contributing to impaired diastolic function. Increased mechanical load due to increased vascular stiffness and direct activation of senescence-associated fibrogenic signals in the myocardium are implicated in the pathogenesis of cardiac fibrosis in the elderly. Reactive oxygen species (ROS), chemokine-mediated recruitment of mononuclear cells and fibroblast progenitors, transforming growth factor (TGF)-β activation, and angiotensin II signaling may be essential mediators of interstitial and perivascular fibrosis in the senescent heart. Reduced collagen degradation may be more important than increased matrix protein synthesis in the pathogenesis of aging-associated fibrosis. In addition to an age-related baseline activation of inflammatory and profibrotic signals, senescence is also associated with a suppressed and prolonged inflammatory reaction after myocardial injury and with defective activation of reparative fibroblasts in response to growth factors. These reparative defects impair scar formation and may promote adverse dilative remodeling. Understanding the involvement of inflammatory and fibrogenic mediators in repair and remodeling of the aging heart is critical in order to design new strategies for prevention of heart failure in elderly patients.

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Acknowledgments

Dr. Frangogiannis’ laboratory is supported by NIH grants R01 HL-76246 and R01 HL-85440, the Wilf Family Cardiovascular Research Institute, and the Edmond J. Safra/Republic National Bank of New York Chair in Cardiovascular Medicine.

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Authors and Affiliations

  1. Department of Medicine (Cardiolology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer G46B, Bronx, NY, 10461, USA

    Arti V. Shinde PhD

  2. Department of Medicine (Cardiolology), Albert Einstein College of Medicine, Bronx, NY, USA

    Nikolaos G. Frangogiannis MD

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  1. Arti V. Shinde PhD
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  2. Nikolaos G. Frangogiannis MD
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Correspondence to Nikolaos G. Frangogiannis MD .

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  1. Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta and Hospitals, Edmonton, Alberta, Canada

    Bodh I. Jugdutt

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Shinde, A.V., Frangogiannis, N.G. (2014). Aging-Associated Alterations in Myocardial Inflammation and Fibrosis: Pathophysiological Perspectives and Clinical Implications. In: Jugdutt, B. (eds) Aging and Heart Failure. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0268-2_24

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  • DOI: https://doi.org/10.1007/978-1-4939-0268-2_24

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