Autophagy in ischemic heart disease

Circ Res. 2009 Jan 30;104(2):150-8. doi: 10.1161/CIRCRESAHA.108.187427.

Abstract

Autophagy is a major catabolic pathway by which mammalian cells degrade and recycle macromolecules and organelles. It plays a critical role in removing protein aggregates, as well as damaged or excess organelles, to maintain intracellular homeostasis and to keep the cell healthy. In the heart, autophagy occurs at low levels under normal conditions, and defects in this process cause cardiac dysfunction and heart failure. However, this pathway is rapidly upregulated under environmental stress conditions, including ATP depletion, reactive oxygen species, and mitochondrial permeability transition pore opening. Although autophagy is enhanced in various pathophysiological conditions, such as during ischemia and reperfusion, the functional role of increased autophagy is not clear and is currently under intense investigation. In this review, we discuss the evidence for autophagy in the heart in response to ischemia and reperfusion, identify factors that regulate autophagy, and analyze the potential roles autophagy might play in cardiac cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis
  • Autophagy*
  • Calcium / metabolism
  • Cell Hypoxia
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / pathology
  • Humans
  • Mitochondria, Heart / enzymology
  • Mitochondria, Heart / pathology*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / pathology*
  • Myocardial Ischemia / prevention & control
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / enzymology
  • Myocardium / pathology*
  • Protein Folding
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Stress, Physiological

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • AMP-Activated Protein Kinases
  • Calcium