ANZAC Research Institute, University of Sydney, Sydney, Australia.
Blood. 2011 Jan 6;117(1):11-20. doi: 10.1182/blood-2010-04-278812. Epub 2010 Sep 27.
Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activation within human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel. A novel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined. We provide evidence of intracoronary up-regulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.
最近的体外研究表明，切应力可以通过非激动剂依赖途径引起血小板活化。然而，尚无研究评估剪切诱导的血小板在人类冠状动脉内的激活程度。我们从接受阿司匹林和氯吡格雷治疗的稳定型冠心病患者的冠状动脉病变近侧和远侧及冠状窦采集血液。开发了一种新的基于计算的技术，可从这些动脉的三维冠状动脉造影图像中估算切应力，并确定狭窄严重程度和计算的切应力对体内血小板和相关白细胞激活途径的影响。我们提供了证据表明，即使同时使用阿司匹林和氯吡格雷，血小板 P-选择素、血小板-单核细胞聚集和单核细胞 CD11b 在冠状动脉内也会上调，而血小板糖蛋白 IIb-IIIa 激活或可溶性 P-选择素上调则不会。这与冠状动脉内狭窄严重程度和计算的切应力相关，并发生在同时使用阿司匹林和氯吡格雷的情况下。我们的结果首次显示剪切相关的血小板和单核细胞在人类冠状动脉内的激活，并提示这是一种潜在的治疗靶点，对传统抗血小板药物有抗性。
