Klinik für Innere Medizin III, Universität des Saarlandes, Kirrberger Strasse, 66421, Homburg, Saar, Germany.
Clin Res Cardiol. 2011 Feb;100(2):147-58. doi: 10.1007/s00392-010-0225-8. Epub 2010 Sep 19.
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.
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).
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.
CD4(+)CD28(null) 细胞代表一种侵袭性和长寿的 T 细胞亚群，能够浸润动脉粥样硬化斑块，导致斑块不稳定，并导致急性冠状动脉综合征（ACS）。本研究旨在评估他汀类药物是否通过凋亡降低 ACS 患者循环中 CD4(+)CD28(null) T 细胞的数量。
将肌钙蛋白阳性 ACS（n = 35）且未接受降胆固醇药物治疗的患者随机分为安慰剂组（n = 17）或每天一次 20mg 瑞舒伐他汀组（n = 18），疗程为 6 周。两组在入组时 CD4(+)CD28(null) T 细胞丰度（>1%）分布均匀（每组 n = 10）。瑞舒伐他汀治疗 72 小时内，CD4(+)CD28(null) T 细胞数量（37×10⁶/L 与安慰剂组 122×10⁶/L，n = 20，P = 0.041）、IFN-γ 产生（62.6%与 101.5%，P = 0.049）和这些 T 细胞凋亡率（63.4%与 12.3%，P<0.001）均显著降低。通过抗凋亡蛋白 B 细胞淋巴瘤 2（BCL-2）的表达来测量内在的线粒体依赖性途径，发现该途径显著下调（平均荧光强度 16.08 与安慰剂组 43.34，P<0.001）。
他汀类药物下调抗凋亡 BCL-2 表达诱导 CD4(+)CD28(null) T 细胞凋亡。在 ACS 中他汀类药物靶向 CD4(+)CD28(null) T 细胞可能提供另一种治疗策略，以预防急性危及生命的冠状动脉事件。
