Platelet Aggregation and Activation under Complex Patterns of Shear Stress

Abstract

SummaryArterial 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 poststenosis 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/cm2 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.

Post-stenotic Recirculating Flow May Cause Hemodynamic Perforator Infarction

“…Furthermore, this region is prone to ischemia and platelet activation, which may lead to cerebral infarction. 11 In the present case, TOF-MRA showed an area with signal intensity remaining lower in the immediate post-stenotic area, though the diameter of the BA lumen was restored. This area well correspond with the area of recirculating flow shown in the PIV experiment.…”

A focus on the role of platelets in liver regeneration: Do platelet-endothelial cell interactions initiate the regenerative process?

“…Platelets exposed to a shear profile containing both high and low shear rates were shown to quickly aggregate, independently of their activation level [27]. Moreover, hemodynamic alterations following PH have been proposed as the start signal for regeneration [28,29].…”

Single-molecule force measurements of the polymerizing dimeric subunit of von Willebrand factor

“…RDVWF (500 μl at 170 ± 40 ng/ml) was exposed to 100 dynes/cm 2 shear stress for 3 min at 37 • C on a cone-andplate viscometer (RS1, HAAKE Instrument Inc., Paramus, NJ), as previously described [15] [Figs. 2(c) and 4].…”