Document Detail


Statins reduce endothelial cell apoptosis via inhibition of TRAIL expression on activated CD4 T cells in acute coronary syndrome.
MedLine Citation:
PMID:  20430391     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Statins reduce cardiovascular-related morbidity and mortality, but their effects on inflammation in atherosclerosis are not fully understood. We investigated whether statins can modulate cytotoxic functions of CD4 T cells in acute coronary syndrome (ACS).
METHODS AND RESULTS: Fresh CD4 T cells were isolated from 55 patients with ACS without statin treatment on admission and from 34 age-matched controls. CD4 T cells collected from ACS patients induced endothelial cell apoptosis significantly more than control T cells. The TNF-related apoptosis-inducing ligand (TRAIL) receptor DR5 was strongly upregulated on endothelial cells, and TRAIL-specific antibodies effectively blocked CD4 T cell-mediated apoptosis, indicating that T cell-mediated endothelial death was dependent on the TRAIL pathway. Expression of both the activating antigen CD69 and TRAIL was enhanced on ACS T cells. In in-vitro assays rosuvastatin, fluvastatin, and pitavastatin directly blocked CD4 T cell-mediated endothelial cell apoptosis and reduced T cell-expression of CD69 and TRAIL through TCR-induced Extracellar signal-Regulated Kinases (ERK) activation.
CONCLUSIONS: Activated CD4 T cells expressing TRAIL are enriched in the blood of ACS patients and induce endothelial injury, which may contribute to the destabilization of the plaque. Early statin therapy may suppress T cell-mediated endothelial cell damage in atherosclerotic plaques and thus prevent cardiovascular events.
Authors:
Kayoko Sato; Toshiyuki Nuki; Keiko Gomita; Cornelia M Weyand; Nobuhisa Hagiwara
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-04
Journal Detail:
Title:  Atherosclerosis     Volume:  213     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-25     Completed Date:  2011-03-07     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  33-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan. msatok@hij.twmu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Acute Coronary Syndrome / drug therapy*,  metabolism*
Aged
Apoptosis*
Atherosclerosis / metabolism
CD4-Positive T-Lymphocytes / cytology*
Endothelial Cells / cytology*
Female
Flow Cytometry / methods
Gene Expression Regulation*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Inflammation
Male
Middle Aged
TNF-Related Apoptosis-Inducing Ligand / metabolism
Grant Support
ID/Acronym/Agency:
P01 HL058000-125166/HL/NHLBI NIH HHS; R01 AG15043/AG/NIA NIH HHS; R01 AI044142-12/AI/NIAID NIH HHS; R01 AI44142/AI/NIAID NIH HHS; R01 AR042527-15/AR/NIAMS NIH HHS; R01 AR41974/AR/NIAMS NIH HHS; R01 AR42527/AR/NIAMS NIH HHS; R01 EY011916-12/EY/NEI NIH HHS; R01 EY11916/EY/NEI NIH HHS; U19 AI57266/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human
Comments/Corrections

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