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DOI: 10.1160/TH05-11-0731
Local delivery of soluble platelet collagen receptor glycoprotein VI inhibits thrombus formation in vivo
Financial support: This work was supported by the Wilhelm-Sander Stiftung (to M.G.) and the Deutsche Forschungsgemeinschaft (Graduiertenkolleg (GRK 794) “Zellbiologische Mechanismen immunassoziierter Prozesse” and “Vaskuläre Medizin” (GRK 438) and MA 2186/3–1 to M.G.).Publication History
Received
09 November 2005
Accepted
05 March 2006
Publication Date:
01 December 2017 (online)


Summary
Platelet-mediated thrombus formation at the site of vascular injury isa major trigger for thrombo-ischemic complications after coronary interventions. The platelet collagen receptor glycoprotein VI (GPVI) plays a critical role in the initiation of arterial thrombus formation. Endothelial denudation of the right carotid artery in rabbits was induced through balloon injury. Subsequently, local delivery of soluble, dimeric fusion protein of GPVI (GPVI-Fc) (n=7) or control Fc (n=7) at the site of vascular injury was performed with a modified double-balloon drugdelivery catheter.Thrombus area within the injured carotid artery was quantified using a computer-assisted image analysis and was used as index of thrombus formation.The extent of thrombus formation was significantly reduced in GPVI-Fc- compared with control Fc-treated carotid arteries (relative thrombus area, GPVI-Fc vs. Fc: 9.3 ± 4.2 vs. 2.3 ± 1.7, p<0.001). Local delivery of soluble GPVI resulted in reduced thrombus formation after catheter-induced vascular injury.These data suggest a selective pharmacological modulation of GPVI-collagen interactions to be important for controlling onset and progression of pathological arterial thrombosis, predominantly or even exclusively at sites of injured carotid arteries in the absence of systemic platelet therapy.