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(Circulation Research. 2008;103:1363.)
© 2008 American Heart Association, Inc.

Reviews

Autophagy in Load-Induced Heart Disease

Beverly A. Rothermel, Joseph A. Hill

From the Departments of Internal Medicine (Cardiology) (B.A.R., J.A.H.) and Molecular Biology (J.A.H.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Joseph A. Hill, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8573. E-mail joseph.hill{at}UTSouthwestern.edu

This review is part of a thematic series on Autophagy, which includes the following articles:

Crosstalk Between Autophagy and Apoptosis in Heart Disease [2008;103:343–351]

Autophagy in Load-Induced Heart Disease

Autophagy in Ischemic Heart Disease

Autophagy in Atherosclerosis: A Cell Survival and Death Phenomenon with Therapeutic Potential
Joseph A. Hill Guest Editor

The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions.

Key Words: autophagy • cardiac hypertrophy • heart failure • hypertrophy • signal transduction

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