Rosuvastatin induces apoptosis in CD4+CD28null T cells in patients with acute coronary syndromes
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Andreas Link Simina Selejan Lisa Hewera Felix Walter Georg Nickenig Michael Bo¨hm
- چاپ و سال / کشور: 2010
Description
Aims CD4?CD28null 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?CD28null T cells by apoptosis in patients with ACS. Methods and 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?CD28null 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?CD28null T cell numbers (37 9 106/L vs. placebo 122 9 106/L, n = 20, P = 0.041), IFN-c 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?CD28null T cells. Targeting CD4?CD28null T cells in ACS statins could provide one further therapeutic strategy to prevent acute life-threatening coronary events.
Clin Res Cardiol (2011) 100:147–158 DOI 10.1007/s00392-010-0225-8 Received: 14 March 2010 / Accepted: 7 September 2010 / Published online: 19 September 2010
