Cadherin 6 Has a Functional Role in Platelet Aggregation and Thrombus Formation

被引：45

作者：

Dunne, Eimear

Spring, Christopher M. ^{[2
]}

Reheman, Adili ^{[2
]}

Jin, Wuxun ^{[2
,3
]}

Berndt, Michael C. ^{[4
]}

Newman, Debra K. ^{[5
]}

Newman, Peter J. ^{[5
]}

Ni, Heyu ^{[2
,3
,6
,7
,8
]}

Kenny, Dermot ^{[1
]}

机构：

[1] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland

[2] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada

[3] Canadian Blood Serv, Toronto, ON, Canada

[4] Dublin City Univ, Biomed Diagnost Inst, Dublin 9, Ireland

[5] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA

[6] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada

[7] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A1, Canada

[8] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2012年 / 32卷 / 07期

基金：

爱尔兰科学基金会;

关键词：

cadherin; 6; alpha IIb beta 3; thrombus formation; platelet aggregation; VON-WILLEBRAND-FACTOR; INTEGRIN ALPHA(IIB)BETA(3); GLYCOPROTEIN-IB; FIBRINOGEN; PROTEINS; RECOGNITION; BINDING; LIGAND; CELLS; ALPHA(E)BETA(7);

D O I：

10.1161/ATVBAHA.112.250464

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective-Thrombosis occurs at sites of vascular injury when platelets adhere to subendothelial matrix proteins and to each other. Platelets express many surface receptor proteins, the function of several of these remains poorly characterized. Cadherin 6 is expressed on the platelet surface and contains an arginine-glycine-aspartic acid motif, suggesting that it might have a supportive role in thrombus formation. The aim of this study was to characterize the role of cadherin 6 in platelet function. Methods and Results-Platelet aggregation was inhibited by both antibodies and exogenous soluble cadherin 6. Platelet adhesion to immobilized cadherin 6 was inhibited by arginine-glycine-aspartic acid-serine tetrapeptides. Antibodies to alpha(IIb)beta 3 inhibited platelet adhesion to cadherin 6. Because platelet aggregation occurs in fibrinogen and von Willebrand factor double-deficient mice, we investigated whether cadherin 6 is an alternative ligand for the integrin alpha(IIb)beta 3. Platelet aggregation in fibrinogen and von Willebrand factor double-deficient mice was significantly inhibited by an antibody to cadherin 6. In flow-based assays, inhibition of cadherin 6 caused a marked reduction in thrombus formation in both human and mouse blood. Conclusion-This study demonstrates the role of cadherin 6 as a novel ligand for alpha(IIb)beta 3 and highlights its function in thrombus formation. (Arterioscler Thromb Vasc Biol. 2012;32:1724-1731.)

引用

页码：1724 / 1731

页数：8

共 32 条

[1] Immunoregulatory functions of KLRG1 cadherin interactions are dependent on forward and reverse signaling [J].