Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction
Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction
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DOI：
10.3109/09537104.2015.1051466
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发表时间：
2016-02-17
期刊：
影响因子：
3.3
通讯作者：
Geisler, Tobias
中科院分区：
文献类型：
--
作者：
Seizer, Peter;Fuchs, Christian;Geisler, Tobias
目的：最近，我们报道了细胞外亲环蛋白A （CyPA）是一种重要的血小板激动剂。尽管可溶性CyPA水平与心血管危险因素相关，但细胞结合的CyPA尚未被研究。在这项研究中，我们首次分析了症状性冠状动脉疾病（CAD）患者血小板结合的CyPA。方法和结果：从388例连续患者中采集血液：204例为稳定型CAD， 184例为急性冠脉综合征（76例为不稳定型心绞痛，78例为非st段抬高型心肌梗死（NSTEMI）， 30例为STEMI）。经典激动剂对血小板的体外刺激显示血小板表面CyPA的表达增强。在稳定的冠心病患者中，血小板结合的CyPA与流式细胞术中p -选择素暴露测量的血小板活性极好地相关。对动脉粥样硬化经典危险因素的分析显示，高血压和高胆固醇血症患者血小板结合CyPA显著增加，而糖尿病和吸烟与血小板表面CyPA结合增加无关。在多变量分析中，高胆固醇血症是血小板结合CyPA升高的唯一显著预测因子。有趣的是，在急性心肌梗死（AMI）患者中，血小板结合的CyPA与稳定的CAD患者相比显著降低。结论：稳定型冠心病患者血小板结合CyPA升高与高血压和高胆固醇血症相关。AMI患者血小板结合CyPA明显降低。
Objective: Recently, we reported that extracellular cyclophilin A (CyPA) is an important agonist for platelets. Whereas soluble CyPA-levels have been associated with cardiovascular risk factors, cell-bound CyPA has not been investigated yet. In this study, we analyzed for the first time platelet-bound CyPA in patients with symptomatic coronary artery disease (CAD). Methods and results: blood was obtained from 388 consecutive patients: 204 with stable CAD and 184 with acute coronary syndrome (76 with unstable angina, 78 with non ST-elevation myocardial infarction (NSTEMI), and 30 with STEMI). In vitro stimulation of platelets with classical agonists revealed an enhanced expression of CyPA on the platelet surface. In patients with stable CAD, platelet-bound CyPA correlated excellently with platelet activity measured by P-selectin exposure in flow cytometry. The analysis of classical risk factors for atherosclerosis revealed that patients with hypertension and hypercholesterolemia had significantly enhanced platelet-bound CyPA, whereas diabetes and smoking were not associated with enhanced CyPA-binding to the platelet surface. In multivariate analysis, hypercholesterolemia was the only significant predictor of enhanced platelet-bound CyPA. Interestingly, in patients with acute myocardial infarction (AMI) platelet-bound CyPA was significantly decreased compared with patients with stable CAD. Conclusions: Enhanced platelet-bound CyPA is associated with hypertension and hypercholesterolemia in stable CAD patients. In patients with AMI platelet-bound CyPA is significantly decreased.