Publication
Title
Everolimus triggers cytokine release by macrophages : rationale for stents eluting everolimus and a glucocorticoid
Author
Abstract
Objective-: Stent-based delivery of the mammalian target of rapamycin (mTOR) inhibitor everolimus is a promising strategy for the treatment of coronary artery disease. We studied potential adverse effects associated with mTOR inhibition. Methods and Results-: Macrophages in culture were either treated with everolimus or starved to inhibit mTOR. Everolimus led to inhibition of protein translation, activation of p38 MAPK, and the release of proinflammatory cytokines (eg, IL-6, TNF[alpha]) and chemokines (eg, MCP1, Rantes) before induction of autophagic death. These effects were also observed with rapamycin, but not after starvation. Everolimus-induced cytokine release was similar in macrophages lacking the essential autophagy gene Atg7 but was inhibited when macrophages were cotreated with p38 MAPK inhibitor SB202190 or the glucocorticoid clobetasol. Combined stent-based delivery of clobetasol and everolimus in rabbit plaques downregulated TNF[alpha] expression as compared with everolimus-treated plaques but did not affect the ability of everolimus to induce macrophage clearance. Conclusion-: mTOR inhibition by everolimus triggers cytokine release in macrophages through inhibition of protein translation and p38 activation. These findings provide a rationale for combined local treatment of atherosclerotic plaques with everolimus and an anti-inflammatory agent.
Language
English
Source (journal)
Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens
Publication
Dallas, Tex. : 2012
ISSN
1079-5642
1524-4636 [online]
Volume/pages
32:5(2012), p. 1228-1235
ISI
000303195100028
Full text (Publisher's DOI)
Full text (publisher's 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 24.04.2012
Last edited 07.09.2017
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