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(Circulation Research. 2009;104:304.)
© 2009 American Heart Association, Inc.

Reviews

Autophagy in Atherosclerosis

A Cell Survival and Death Phenomenon With Therapeutic Potential

Wim Martinet, Guido R.Y. De Meyer

From the Division of Pharmacology, University of Antwerp, Belgium.

Correspondence to Dr Wim Martinet, Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. E-mail wim.martinet{at}ua.ac.be

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 [2008;103:1363–1369]

Autophagy in Ischemic Heart Disease [2008;104:000-000]

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

Autophagy is a reparative, life-sustaining process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. A growing body of evidence suggests that autophagy is stimulated in advanced atherosclerotic plaques by oxidized lipids, inflammation, and metabolic stress conditions. However, despite the increasing interest in autophagy in various pathophysiological situations such as neurodegeneration, cancer, and cardiac myopathies, the process remains an underestimated and overlooked phenomenon in atherosclerosis. As a consequence, its role in plaque formation and stability is poorly understood. Most likely, autophagy safeguards plaque cells against cellular distress, in particular oxidative injury, by degrading damaged intracellular material. In this way, autophagy is antiapoptotic and contributes to cellular recovery in an adverse environment. An interesting observation is that basal autophagy can be intensified by specific drugs. Excessively stimulated autophagic activity is capable of destroying major proportions of the cytosol, leading finally to type II programmed cell death that lacks several hallmarks of apoptosis or necrosis. Because atherosclerosis is an inflammatory disorder of the arterial intima, pharmacological approaches could be developed to stabilize vulnerable, rupture-prone lesions through selective induction of macrophage autophagic death.

Key Words: atherosclerosis • autophagy • autophagosome • lysosome • cell death