Role of autophagy in heart failure associated with aging.
Heart failure is a progressive disease, leading to reduced quality of life and premature death. Adverse ventricular remodeling involves changes in the balance between cardiomyocyte protein synthesis and degradation, forcing these myocytes in equilibrium between life and death. In this context, autophagy has been recognized to play a role in the pathophysiology of heart failure. At basal levels, autophagy performs housekeeping functions, maintaining cardiomyocyte function and ventricular mass. Autophagy also occurs in the failing human heart, and upregulation has been reported in animal models of pressure overload-induced heart failure. Although the factors that determine whether autophagy will be protective or detrimental are not well known, the level and duration of autophagy seem important. Autophagy may antagonize ventricular hypertrophy by increasing protein degradation, which decreases tissue mass. However, the rate of protective autophagy declines with age. The inability to remove damaged structures results in the progressive accumulation of 'garbage', including abnormal intracellular proteins aggregates and undigested materials such as lipofuscin. Eventually, the progress of these changes results in enhanced oxidative stress, decreased ATP production, collapse of the cellular catabolic machinery, and cell death. By contrast, in load-induced heart failure, the extent of autophagic flux can rise to maladaptive levels. Excessive autophagy induction leads to autophagic cell death and loss of cardiomyocytes and may contribute to the worsening of heart failure. Accordingly, the development of therapies that up-regulate the repair qualities of the autophagic process and down-regulate the cell death aspects would be of great value in the treatment of heart failure.
De Meyer
Guido R Y
GR
Division of Pharmacology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. guido.demeyer@ua.ac.be
De Keulenaer
Gilles W
GW
Martinet
Wim
W
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000367:Age Factors; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy; D001530:Belgium / Q000453:epidemiology; D018450:Disease Progression; D006333:Heart Failure / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D018384:Oxidative Stress; D015995:Prevalence; D012084:Renin-Angiotensin System / Q000187:drug effects
D000255:Adenosine Triphosphate
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