Gori A M, Cesari F, Marcucci R, Giusti B, Paniccia R, Antonucci E, Gensini G F, Abbate R
Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
Atherosclerosis. 2009 Jan;202(1):255-62. doi: 10.1016/j.atherosclerosis.2008.04.001. Epub 2008 Apr 11.
Residual platelet reactivity (RPR) on antiplatelet therapy in ischemic heart disease patients is associated with adverse events. Clinical, cellular and pharmacogenetic factors may account for the variable response to antiplatelet treatment.
We sought to explore the interplay of multiple pro-inflammatory and anti-inflammatory cytokines with platelet function in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy.
In 208 ACS patients undergoing PCI on dual antiplatelet therapy we measured platelet function by platelet aggregation with two agonists [1mM arachidonic acid (AA) and 10muM ADP]. IL-1beta, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, TNF-alpha, and VEGF levels were determined by using the Bio-Plex cytokine assay (Bio-Rad Laboratories Inc., Hercules, CA, USA). We defined patients with RPR those with platelet aggregation by AA >or=20% and/or ADP (10micromol) >or=70%.
We documented a significant association between IP-10, IFN-gamma, IL-4 and RPR by both AA- and ADP-induced platelet aggregation after adjustment for age, sex, cardiovascular risk factors, ejection fraction, BMI, vWF and CRP. Patients with pro-inflammatory cytokines not compensated by anti-inflammatory cytokines had higher risk of RPR by both AA and ADP (AA: OR=3.85, 95% CI 1.52-9.74; ADP: OR=2.49, 95% CI 1.33-4.68) with respect to patients with balanced anti-/pro-inflammatory cytokines. Patients with anti-inflammatory response overwhelming pro-inflammatory response have lower risk of RPR (AA: OR=0.55, 95% CI 0.28-1.06; ADP: OR=0.47, 95% CI 0.26-0.87).
Our study provides new insights into the interplay of anti-/pro-inflammatory cytokines with platelet hyper-reactivity in high-risk patients.
缺血性心脏病患者抗血小板治疗中的残余血小板反应性（RPR）与不良事件相关。临床、细胞和药物遗传学因素可能解释抗血小板治疗反应的差异。
我们试图探讨在接受经皮冠状动脉介入治疗（PCI）并采用双重抗血小板治疗的急性冠状动脉综合征（ACS）患者中，多种促炎和抗炎细胞因子与血小板功能之间的相互作用。
在208例接受双重抗血小板治疗的PCI的ACS患者中，我们通过用两种激动剂[1mM花生四烯酸（AA）和10μM二磷酸腺苷（ADP）]诱导血小板聚集来测量血小板功能。采用Bio-Plex细胞因子检测法（美国加利福尼亚州赫尔克里士市伯乐公司）测定白细胞介素-1β（IL-1β）、白细胞介素-1受体拮抗剂（IL-1ra）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-12（IL-12）、干扰素γ诱导蛋白10（IP-10）、干扰素γ（IFN-γ）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1α（MIP-1α）、巨噬细胞炎性蛋白-1β（MIP-1β）、肿瘤坏死因子-α（TNF-α）和血管内皮生长因子（VEGF）水平。我们将AA诱导的血小板聚集≥20%和/或ADP（10μmol）诱导的血小板聚集≥70%的患者定义为有RPR的患者。
在对年龄、性别、心血管危险因素、射血分数、体重指数、血管性血友病因子（vWF）和C反应蛋白（CRP）进行校正后，我们发现IP-10、IFN-γ、IL-4与AA和ADP诱导的血小板聚集后的RPR之间存在显著关联。与促炎和抗炎细胞因子平衡的患者相比，促炎细胞因子未被抗炎细胞因子代偿的患者发生AA和ADP诱导的RPR的风险更高（AA：比值比[OR]=3.85，95%置信区间[CI]1.52-9.74；ADP：OR=2.49，95%CI 1.33-4.68）。抗炎反应超过促炎反应的患者发生RPR的风险较低（AA：OR=0.55，95%CI 0.28-1.06；ADP：OR=0.47，95%CI 0.26-0.87）。
我们的研究为高危患者中促炎/抗炎细胞因子与血小板高反应性之间的相互作用提供了新的见解。
