Cross-Linking GPVI-Fc by Anti-Fc Antibodies Potentiates Its Inhibition of Atherosclerotic Plaque- and Collagen-Induced Platelet Activation

• Main Authors: Janina Jamasbi, RPh, Remco T.A. Megens, PhD, Mariaelvy Bianchini, MSc, Kerstin Uhland, PhD, Götz Münch, MD, Martin Ungerer, MD, Shachar Sherman, BSc, Alexander Faussner, PhD, Richard Brandl, MD, Christine John, MSc, Johannes Buchner, PhD, Christian Weber, MD, Reinhard Lorenz, MD, Natalie Elia, PhD, Wolfgang Siess, MD
• Format: Article
• Language: English
• Published: Elsevier 2016-04-01
• Series: JACC: Basic to Translational Science
• Subjects: antithrombotic; atherothrombosis; glycoprotein VI; plaque rupture
• Online Access: http://www.sciencedirect.com/science/article/pii/S2452302X16000437

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.