Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 6, Issue 12, Pages 2132-2142Publisher
WILEY
DOI: 10.1111/j.1538-7836.2008.03167.x
Keywords
collagen; glycoprotein VI; integrin alpha(2)beta(1); thrombus; von Willebrand factor
Categories
Funding
- European Commission [2005-020 706-3]
- UK Medical Research Council
- British Heart Foundation
- Netherlands Organization for Scientific Research [114 000 076]
- Academy of Finland
- Medical Research Council [G0500707] Funding Source: researchfish
- MRC [G0500707] Funding Source: UKRI
Ask authors/readers for more resources
Background: Collagen acts as a potent surface for platelet adhesion and thrombus formation under conditions of blood flow. Studies using collagen-derived triple-helical peptides have identified the GXX'GER motif as an adhesive ligand for platelet integrin alpha 2 beta 1, and (GPO)(n) as a binding sequence for the signaling collagen receptor, glycoprotein VI (GPVI). Objective: The potency was investigated of triple-helical peptides, consisting of GXX'GER sequences within (GPO)(n) or (GPP)(n) motifs, to support flow-dependent thrombus formation. Results: At a high-shear rate, immobilized peptides containing both the high-affinity alpha 2 beta 1-binding motif GFOGER and the (GPO)(n) motif supported platelet aggregation and procoagulant activity, even in the absence of von Willebrand factor (VWF). With peptides containing only one of these motifs, co-immobilized VWF was needed for thrombus formation. The (GPO)(n) but not the (GPP)(n) sequence induced GPVI-dependent platelet aggregation and procoagulant activity. Peptides with intermediate affinity (GLSGER, GMOGER) or low-affinity (GASGER, GAOGER) alpha 2 beta 1-binding motifs formed procoagulant thrombi only if both (GPO)(n) and VWF were present. At a low-shear rate, immobilized peptides with high- or low-affinity alpha 2 beta 1-binding motifs mediated formation of thrombi with procoagulant platelets only in combination with (GPO)(n). Conclusions: Triple-helical peptides with specific receptor-binding motifs mimic the properties of native collagen I in thrombus formation by binding to both platelet collagen receptors. At a high-shear rate, either GPIb or high-affinity (but not low-affinity) GXX'GER mediates GPVI-dependent formation of procoagulant thrombi. By extension, high-affinity binding for alpha 2 beta 1 can control the overall platelet-adhesive activity of native collagens.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available