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

  • Arti V. Shinde
  • Nikolaos G. Frangogiannis
Chapter

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.

Keywords

Diastolic Dysfunction Cardiac Fibroblast Cardiac Fibrosis Infarcted Heart Cardiomyocyte Hypertrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Medicine (Cardiolology)Albert Einstein College of MedicineBronxUSA
  2. 2.Department of Medicine (Cardiolology)Albert Einstein College of MedicineBronxUSA

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