Wagner C T, Kroll M H, Chow T W, Hellums J D, Schafer A I
Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX 77251, USA.
Biorheology. 1996 May-Jun;33(3):209-29. doi: 10.1016/0006-355X(96)00018-2.
Elevated shear stress levels in pathologically stenosed vessels induce platelet activation and aggregation, and may play a role in the pathogenesis of arterial disease. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This study was designed to examine the synergistic interaction of shear stress and epinephrine in the activation of platelets. Platelets (in PRP) sheared at 60 dyn/cm2 showed little or no aggregation unless pretreated with epinephrine. Pretreatment with 250 nM epinephrine followed by shear at 60 dyn/cm2 induced > 60% platelet aggregation. The specific alpha 2-adrenergic receptor antagonist yohimbine inhibited the synergistic aggregation, as did the ADP scavenging system phosphocreatine/creatine phosphokinase, indicating a three-way synergism with ADP. Chemical or monoclonal antibody blockade of von Willebrand factor (vWF) interactions with either platelet glycoprotein (Gp) Ib or Gp IIb/IIIa completely inhibited platelet aggregation induced by activating levels of shear stress alone. However, the combination of epinephrine and shear stress induced platelet aggregation that was blocked by 10E5, a monoclonal antibody that inhibits vWF binding to Gp IIb/IIIa, but not by aurin tricarboxylic acid or the monoclonal antibody 6D1, both of which inhibit vWF binding to Gp Ib. Synergistic platelet aggregation in response to epinephrine and shear stress was observed in washed platelets, platelet-rich plasma and whole blood in vitro, and also ex vivo following exercise to elevate endogenous levels of catecholamines. These results indicate that epinephrine synergizes with shear stress to induce platelet aggregation. This synergistic response requires functional Gp IIb/IIIa complexes, but is at least partially independent of vWF-Gp Ib interactions.
病理性狭窄血管中升高的剪切应力水平会诱导血小板活化和聚集，并可能在动脉疾病的发病机制中起作用。血浆儿茶酚胺浓度升高也与急性冠状动脉缺血综合征的发作有关。本研究旨在探讨剪切应力和肾上腺素在血小板活化中的协同相互作用。在60达因/平方厘米剪切力作用下的血小板（在富血小板血浆中）几乎没有或没有聚集，除非用肾上腺素预处理。用250 nM肾上腺素预处理，然后在60达因/平方厘米剪切力作用下，可诱导超过60%的血小板聚集。特异性α2-肾上腺素能受体拮抗剂育亨宾抑制了协同聚集，ADP清除系统磷酸肌酸/肌酸磷酸激酶也有此作用，表明与ADP存在三方协同作用。用化学方法或单克隆抗体阻断血管性血友病因子（vWF）与血小板糖蛋白（Gp）Ib或Gp IIb/IIIa的相互作用，可完全抑制仅由激活水平的剪切应力诱导的血小板聚集。然而，肾上腺素和剪切应力的组合诱导的血小板聚集被10E5阻断，10E5是一种抑制vWF与Gp IIb/IIIa结合的单克隆抗体，但不被金精三羧酸或单克隆抗体6D1阻断，这两种抗体均抑制vWF与Gp Ib的结合。在体外的洗涤血小板、富血小板血浆和全血中，以及在运动后体内儿茶酚胺内源性水平升高的情况下，均观察到肾上腺素和剪切应力引起的协同血小板聚集。这些结果表明，肾上腺素与剪切应力协同诱导血小板聚集。这种协同反应需要功能性的Gp IIb/IIIa复合物，但至少部分独立于vWF-Gp Ib相互作用。
