Autophagy in load-induced heart disease

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1363-1369
Number of pages7
JournalCirculation Research
Volume103
Issue number12
DOIs
StatePublished - Dec 5 2008

Fingerprint

Autophagy
Cardiac Myocytes
Heart Diseases
Disease Progression
Proteins
Pressure
Ventricular Remodeling
Workload
Cardiac Output
Energy Metabolism
Plastics
Dilatation
Heart Failure
Hemodynamics
Myocardial Infarction
Hypertension
Growth

Keywords

  • Autophagy
  • Cardiac hypertrophy
  • Heart failure
  • Hypertrophy
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Autophagy in load-induced heart disease. / Rothermel, Beverly A; Hill, Joseph A.

In: Circulation Research, Vol. 103, No. 12, 05.12.2008, p. 1363-1369.

Research output: Contribution to journalArticle

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