Cadherin 6 has a functional role in platelet aggregation and thrombus formation. Arterioscler Thromb Vasc Biol 2012 Jul;32(7):1724-31
Date
04/28/2012Pubmed ID
22539596Pubmed Central ID
PMC4155514DOI
10.1161/ATVBAHA.112.250464Scopus ID
2-s2.0-84865282307 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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 DAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinPeter 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 SequenceAnimals
Blood Platelets
Cadherins
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligopeptides
Platelet Adhesiveness
Platelet Aggregation
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombosis