title: Cross-Linking GPVI-Fc by Anti-Fc Antibodies Potentiates Its Inhibition of Atherosclerotic Plaque- and Collagen-Induced Platelet Activation.
abstract: To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc), the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG). Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes. Cross-linking of GPVI into oligomeric complexes provides a new, highly effective, and probably safe antithrombotic treatment as it suppresses platelet GPVI-plaque interaction selectively at the site of acute atherothrombosis.
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Jamasbi
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Remco T A
authors.initials: RT
authors.lastname: Megens
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany.
authors.forename: Mariaelvy
authors.initials: M
authors.lastname: Bianchini
authors.affiliation: advanceCOR GmbH, Munich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Uhland
authors.affiliation: advanceCOR GmbH, Munich, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Münch
authors.affiliation: advanceCOR GmbH, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ungerer
authors.affiliation: Department of Life Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Shachar
authors.initials: S
authors.lastname: Sherman
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
authors.affiliation: St. Mary's Square Institute for Vascular Surgery and Phlebology, Munich, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Brandl
authors.affiliation: Department of Biotechnology, Technical University of Munich, Garching, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: John
authors.affiliation: Department of Biotechnology, Technical University of Munich, Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lorenz
authors.affiliation: Department of Life Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Elia
authors.affiliation: Institute for the Prevention of Cardiovascular Diseases, University of Munich (LMU Munich), Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Siess
keywords: Fc, fragment crystallizable; GPVI, glycoprotein VI; IgG, immunoglobulin G; PE, phycoerythrin; SIM, structured illumination microscopy; STED, stimulated emission depletion; XL, cross-linked; antithrombotic; atherothrombosis; glycoprotein VI; plaque rupture