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FoxO, Autophagy, and Cardiac Remodeling

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Abstract

In response to changes in workload, the heart grows or shrinks. Indeed, the myocardium is capable of robust and rapid structural remodeling. In the setting of normal, physiological demand, the heart responds with hypertrophic growth of individual cardiac myocytes, a process that serves to maintain cardiac output and minimize wall stress. However, disease-related stresses, such as hypertension or myocardial infarction, provoke a series of changes that culminate in heart failure and/or sudden death. At the other end of the spectrum, cardiac unloading, such as occurs with prolonged bed rest or weightlessness, causes the heart to shrink. In recent years, considerable strides have been made in deciphering the molecular and cellular events governing pro- and anti-growth events in the heart. Prominent among these mechanisms are those mediated by FoxO (Forkhead box-containing protein, O subfamily) transcription factors. In many cell types, these proteins are critical regulators of cell size, viability, and metabolism, and their importance in the heart is just emerging. Also in recent years, evidence has emerged for a pivotal role for autophagy, an evolutionarily conserved pathway of lysosomal degradation of damaged proteins and organelles, in cardiac growth and remodeling. Indeed, evidence for activated autophagy has been detected in virtually every form of myocardial disease. Now, it is clear that FoxO is an upstream regulator of both autophagy and the ubiquitin-proteasome system. Here, we discuss recent advances in our understanding of cardiomyocyte autophagy, its governance by FoxO, and the roles each of these plays in cardiac remodeling.

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Acknowledgements

We thank Drs. Sergio Lavandero and Thomas Gillette for critical reading of the manuscript.

Source of Funding

This work was supported by grants from the NIH (HL-075173; HL-080144; HL-090842), AHA (0640084N), ADA (7-08-MN-21-ADA), and the AHA-Jon Holden DeHaan Foundation (0970518N).

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  1. Department of Internal Medicine (Division of Cardiology), University of Texas Southwestern Medical Center, NB11.200, 6000 Harry Hines Boulevard, Dallas, TX, 75390-8573, USA

    Anwarul Ferdous, Pavan K. Battiprolu, Yan G. Ni & Beverly A. Rothermel

  2. Department of Internal Medicine (Division of Cardiology) and Department of Molecular Biology, University of Texas Southwestern Medical Center, NB11.200, 6000 Harry Hines Boulevard, Dallas, TX, 75390-8573, USA

    Joseph A. Hill

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  1. Anwarul Ferdous
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Ferdous, A., Battiprolu, P.K., Ni, Y.G. et al. FoxO, Autophagy, and Cardiac Remodeling. J. of Cardiovasc. Trans. Res. 3, 355–364 (2010). https://doi.org/10.1007/s12265-010-9200-z

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