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A novel anti-platelet peptide (Z4A5) potential for glycoprotein IIb/IIIa inhibits platelet aggregation.

Abstract：

INTRODUCTION:Z4A5 is a novel peptide that inhibits platelet aggregation and formation of platelet thrombi, but the mechanism of its anti-platelet effects remains unknown. This study explores the anti-platelet effect and mechanism of Z4A5. METHODS:We investigated the anti-platelet activity of Z4A5 on platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (TH) in human platelet-rich plasma (PRP). Fibrinogen and PAC-1 binding to glycoproteinIIb/IIIa (GPIIb/IIIa) were measured by flow cytometry. In addition, we investigated the integrin specificity of Z4A5 in attachment and detachment assays using human umbilical vein endothelial cells (HUVEC) and assessed the relative cell number using the MTT assay. RESULTS:In vitro, Z4A5 inhibited ADP-, AA- and TH-induced human platelet aggregation with IC(50) values of 0.46 ± 0.05 μM (n = 10), 0.23 ± 0.0 5 μM (n = 10) and 0.21 ± 0.02 μM (n = 10), respectively. Z4A5 inhibited fibrinogen, and PAC-1 bound to platelet GPIIb/IIIa with IC(50) values of 0.48 ± 0.07 μM (n = 8) and 0.63 ± 0.12 μM (n = 6), respectively. Z4A5 failed to inhibit α(V)β(3) integrin-mediated HUVEC attachment to vitronectin and did not cause any significant detachment of HUVEC monolayer when compared with the controls. CONCLUSIONS:Z4A5 is a potential anti-platelet drug that inhibits fibrinogen binding to GPIIb/IIIa, but does not affect the structurally similar integrin α(V)β(3).

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Li YX,Sun Q,Zhang H,Ren ST,Liao YR,Wang Y,Shen XL,Wang B

doi

10.1016/j.thromres.2012.02.047

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

e217-22

issue

5

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(12)00095-3

journal_volume

129

pub_type

杂志文章

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