title: Rosuvastatin induces apoptosis in CD4(+)CD28 (null) T cells in patients with acute coronary syndromes.
abstract: OBJECTIVE
  CD4(+)CD28(null) cells represent an aggressive and long-living T cell subpopulation, capable of infiltrating atheromatous plaque, leading to destabilisation and resulting in acute coronary syndromes (ACS). The aim of this study was to evaluate whether statins decrease the number of circulating CD4(+)CD28(null) T cells by apoptosis in patients with ACS.
  
  
  RESULTS
  Patients with troponin-positive ACS (n = 35) without cholesterol lowering drugs were randomised to placebo (n = 17) or rosuvastatin 20 mg (n = 18) once daily for 6 weeks. CD4(+)CD28(null) T cell abundance (>1%) was distributed equally among the two groups at entry (n = 10 per group). Within 72 h rosuvastatin treatment significantly reduced mean CD4(+)CD28(null) T cell numbers (37 × 10⁶/L vs. placebo 122 × 10⁶/L, n = 20, P = 0.041), IFN-γ production (62.6 vs. 101.5%, P = 0.049) and increased apoptosis of these T cells (63.4 vs. 12.3%, P < 0.001). The intrinsic mitochondria-dependent pathway measured by the anti-apoptotic protein expression of B cell lymphoma 2 (BCL-2) was significantly down-regulated (mean fluorescence intensity 16.08 vs. placebo 43.34, P < 0.001).
  
  
  CONCLUSIONS
  The down-regulation of anti-apoptotic BCL-2 expression by statins induces apoptosis in CD4(+)CD28(null) T cells. Targeting CD4(+)CD28(null) T cells in ACS statins could provide one further therapeutic strategy to prevent acute life-threatening coronary events.
authors.affiliation: Klinik für Innere Medizin III, Universität des Saarlandes, Kirrberger Strasse, 66421, Homburg, Saar, Germany. andreas.link@uks.eu
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
authors.forename: Simina
authors.initials: S
authors.lastname: Selejan
authors.forename: Lisa
authors.initials: L
authors.lastname: Hewera
authors.forename: Felix
authors.initials: F
authors.lastname: Walter
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium