Zhang Jian-ning, Bergeron Angela L, Yu Qinghua, Sun Carol, McIntire Larry V, López José A, Dong Jing-fei
The Division of Thrombosis Research, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Thromb Haemost. 2002 Nov;88(5):817-21.
Arterial stenosis results in a complex pattern of blood flow containing an extremely fast flow in the throat of stenosis and a post-stenosis low flow. The fast flow generates high shear stress that has been demonstrated in vitro to activate and aggregate platelets. One potential problem of these in vitro studies is that platelets are invariably exposed to a high shear stress for a period that is significantly longer than they would have experienced in vivo. More importantly, the role of the post-stenosis low flow in platelet activation and aggregation has not been determined. By exposing platelets to a shear profile that contains both high and low shear segments, we found that platelets aggregate when they are exposed to a high shear stress of 100 dyn/cm(2) for as short as 2.5 s, a period that is significantly shorter than those previously reported (30-120 s). Platelet aggregation under this condition requires a low shear exposure immediately after a high shear pulse, suggesting that post-stenosis low flow enhances platelet aggregation. Furthermore, platelet aggregation under this condition is not activation-dependent because the CD62P expression of sheared platelets is significantly less than that of platelets treated with ADP. Based on these findings, we propose that shear-induced platelet aggregation may be a process of mechanical crosslinking of platelets, requiring minimal platelet activation. This process may function as a protective mechanism to prevent in vivo irreversible platelet activation and aggregation under temporary high shear.
动脉狭窄会导致复杂的血流模式，包括狭窄部位喉部的极快速血流以及狭窄后低血流。快速血流会产生高剪切应力，体外实验已证明这种高剪切应力会激活血小板并使其聚集。这些体外研究的一个潜在问题是，血小板总是会在高剪切应力下暴露很长一段时间，这比它们在体内所经历的时间长得多。更重要的是，狭窄后低血流在血小板激活和聚集中的作用尚未确定。通过让血小板暴露于包含高剪切段和低剪切段的剪切模式下，我们发现，血小板在暴露于100达因/平方厘米的高剪切应力下仅2.5秒时就会聚集，这一时间段明显短于先前报道的时间（30 - 120秒）。在这种情况下，血小板聚集需要在高剪切脉冲后立即进行低剪切暴露，这表明狭窄后低血流会增强血小板聚集。此外，在这种情况下的血小板聚集并不依赖于激活，因为剪切后血小板的CD62P表达明显低于用ADP处理的血小板。基于这些发现，我们提出剪切诱导的血小板聚集可能是血小板机械交联的过程，所需的血小板激活极少。这一过程可能作为一种保护机制，以防止体内血小板在暂时的高剪切下发生不可逆的激活和聚集。
