Publication
Title
Drug-induced macrophage autophagy in atherosclerosis : for better or worse?
Author
Abstract
Autophagy is a reparative, life-sustaining process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. Mice with a macrophage-specific deletion of the essential autophagy gene Atg5 develop plaques with increased apoptosis and oxidative stress as well as enhanced plaque necrosis. This finding indicates that basal autophagy in macrophages is anti-apoptotic and present in atherosclerotic plaques to protect macrophages against various atherogenic stressors. However, autophagy is impaired in advanced stages of atherosclerosis and its deficiency promotes atherosclerosis in part through activation of the inflammasome. Because basal autophagy can be intensified selectively in macrophages by specific drugs such as mammalian target of rapamycin (mTOR) inhibitors or Toll-like receptor 7 (TLR7) ligands, these drugs were recently tested as potential plaque stabilizing compounds. Stent-based delivery of the mTOR inhibitor everolimus promotes a stable plaque phenotype, whereas local administration of the TLR7 ligand imiquimod stimulates inflammation and plaque progression. Therefore, more drugs capable of inducing autophagy should be tested in plaque macrophages to evaluate the feasibility of this approach. Given that drug-induced macrophage autophagy is associated with pro-inflammatory responses due to cytokine release, induction of postautophagic necrosis or activation of phagocytes after clearance of the autophagic corpse, cotreatment with anti-inflammatory compounds may be required. Overall, this review highlights the pros and cons of macrophage autophagy as a drug target for plaque stabilization.
Language
English
Source (journal)
Basic research in cardiology. - Darmstadt
Publication
Darmstadt : 2013
ISSN
0300-8428
Volume/pages
108:1(2013), p. 1-11
Article Reference
321
ISI
000314641700013
Medium
E-only publicatie
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 07.01.2013
Last edited 26.04.2017
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