FIBRINOLYSIS INHIBITS SHEAR STRESS-INDUCED PLATELET-AGGREGATION

被引:22
作者
KAMAT, SG
MICHELSON, AD
BENOIT, SE
MOAKE, JL
RAJASEKHAR, D
HELLUMS, JD
KROLL, MH
SCHAFER, AI
机构
[1] VET AFFAIRS MED CTR, MED SERV, HOUSTON, TX 77030 USA
[2] RICE UNIV, HOUSTON, TX 77030 USA
[3] UNIV MASSACHUSETTS, SCH MED, WORCESTER, MA USA
[4] MED CTR CENT MASSACHUSETTS, WORCESTER, MA USA
关键词
STRESS; SHEAR; ENZYMES; PLASMINOGEN ACTIVATORS; PLATELETS;
D O I
10.1161/01.CIR.92.6.1399
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Shear stress-induced platelet aggregation may initiate arterial thrombosis at sites of pathological blood flow. Shear stress-induced platelet aggregation is mediated by von Willebrand factor (vWf) binding to platelet membrane glycoprotein (GP) Ib and GP IIb/IIIa. Tissue-type plasminogen activator (TPA) induces thrombolysis in coronary arteries through the local generation of plasmin. Plasmin also proteolyses GP Ib and plasma vWf. Methods and Results Because these effects could mitigate shear stress-induced platelet aggregation, we investigated the effect of fibrinolytic agents on platelet aggregation in response to a pathological shear stress of 120 dynes/cm(2) generated by a cone-and-platen rotational viscometer. Plasmin inhibited shear stress-induced aggregation of washed platelets, and this was associated with a decrease in GP Ib. TPA, at concentrations greater than or equal to 2000 IU/mL, significantly inhibited shear stress-induced platelet aggregation of platelet-rich plasma without a decrease in platelet GP Ib. In plasma-platelet mixing experiments, we determined that the TPA effect was localized to plasma. Purified vWf multimer degradation by TPA (in the presence of exogenous plasminogen) was associated with the loss of the capacity of vWf to support shear stress-induced platelet aggregation. Conclusions These results demonstrate that TPA inhibits platelet aggregation in response to pathological shear stress by altering the multimeric composition of vWf. This effect of TPA on shear stress-induced platelet aggregation may contribute, along with fibrinolysis, to the therapeutic effect of TPA in restoring blood flow during acute coronary artery thrombosis.
引用
收藏
页码:1399 / 1407
页数:9
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