title: Statins reduce endothelial cell apoptosis via inhibition of TRAIL expression on activated CD4 T cells in acute coronary syndrome.
abstract: 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).
  
  
  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.affiliation: Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan. msatok@hij.twmu.ac.jp
authors.forename: Kayoko
authors.initials: K
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nuki
authors.forename: Keiko
authors.initials: K
authors.lastname: Gomita
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Weyand
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Hagiwara
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D000368:Aged; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human