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Cadherin 6 has a functional role in platelet aggregation and thrombus formation. Arterioscler Thromb Vasc Biol 2012 Jul;32(7):1724-31

Date

04/28/2012

Pubmed ID

22539596

Pubmed Central ID

PMC4155514

DOI

10.1161/ATVBAHA.112.250464

Scopus ID

2-s2.0-84865282307 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

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 α(IIb)β(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 α(IIb)β(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.

CONCLUSIONS: This study demonstrates the role of cadherin 6 as a novel ligand for α(IIb)β(3) and highlights its function in thrombus formation.

Author List

Dunne E, Spring CM, Reheman A, Jin W, Berndt MC, Newman DK, Newman PJ, Ni H, Kenny D

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Peter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Blood Platelets
Cadherins
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligopeptides
Platelet Adhesiveness
Platelet Aggregation
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombosis