TY  - JOUR
A1  - Han, Chao
A1  - Ren, Pengxuan
A1  - Mamtimin, Medina
A1  - Kruk, Linus
A1  - Sarukhanyan, Edita
A1  - Li, Chenyu
A1  - Anders, Hans-Joachim
A1  - Dandekar, Thomas
A1  - Krueger, Irena
A1  - Elvers, Margitta
A1  - Goebel, Silvia
A1  - Adler, Kristin
A1  - Münch, Götz
A1  - Gudermann, Thomas
A1  - Braun, Attila
A1  - Mammadova-Bach, Elmina
T1  - Minimal collagen-binding epitope of glycoprotein VI in human and mouse platelets
JF  - Biomedicines
N2  - Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predict a minimal collagen-binding epitope of GPVI dimer and designed an EA-20 antibody that recognizes a linear epitope of this surface. Using platelets and whole blood samples donated from wild-type and humanized GPVI transgenic mice and also humans, our experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin. The EA-20 antibody also prevents thrombus formation in whole blood, on the collagen-coated surface, in arterial flow conditions. We also show that EA-20 does not influence GPVI clustering or receptor shedding. Therefore, we propose that blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach by inhibiting specific interactions between GPVI and the collagen matrix.
KW  - GPVI
KW  - collagen
KW  - blood platelets
KW  - thrombosis
KW  - anti-thrombotic therapies
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304148
SN  - 2227-9059
VL  - 11
IS  - 2
ER  -