Autophagy in atherosclerosis.
Autophagy is a catabolic pathway for bulk destruction of long-lived proteins and organelles via lysosomes. Basal autophagy represents a reparative, life-sustaining process, but unrestrained autophagic activity promotes cell death. A growing body of evidence suggests that autophagy occurs in advanced atherosclerotic plaques. Vascular smooth muscle cells, macrophages, or endothelial cells treated in vitro with proatherogenic stimuli reveal certain features typical of autophagy, such as LC3 processing, formation of myelin figures, and extensive vacuolization. However, despite the increasing interest in autophagy, its role in atherosclerosis remains poorly understood. Most likely, autophagy safeguards plaque cells against cellular distress, in particular oxidative injury, by degrading the damaged intracellular material. In this way, autophagy is antiapoptotic and contributes to cellular recovery in an adverse environment. Because atherosclerosis is an inflammatory disorder of the arterial intima, pharmacologic approaches have recently been developed to stabilize vulnerable, rupture-prone lesions through selective induction of macrophage autophagic death.
Martinet
Wim
W
Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. wim.martinet@ua.ac.be
De Meyer
Guido R Y
GR
D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D002317:Cardiovascular Agents; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases