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http://purl.uniprot.org/citations/15505105http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15505105http://www.w3.org/2000/01/rdf-schema#comment"

Background

Platelet inhibition is a major strategy to prevent arterial thrombosis, but it is frequently associated with increased bleeding because of impaired primary hemostasis. The activating platelet collagen receptor, glycoprotein VI (GP VI), may serve as a powerful antithrombotic target because its inhibition or absence results in profound protection against arterial thrombosis but no major bleeding in mice.

Methods and results

Mice lacking (-/-) or expressing half-levels (+/-) of the other major platelet collagen receptor, integrin alpha2beta1, were injected with the anti-GP VI antibody JAQ1 and analyzed on day 5. Anti-GP VI treatment resulted in a marked hemostatic defect in alpha2-/- or alpha2+/-mice, as shown by dramatically prolonged tail bleeding times. Platelet adhesion to collagen was studied in an ex vivo whole-blood perfusion system under high shear conditions. Weak integrin activation by thromboxane A2 (TxA2) receptor stimulation restored defective adhesion of anti-GP VI-treated wild-type but not alpha2-/- or alpha2+/-platelets to collagen. This process required the simultaneous activation of the G(q) and G13 signaling pathways, as demonstrated by use of the respective knockout strains. Conversely, inhibition of TxA2 production by aspirin severely compromised hemostasis in anti-GP VI-treated or GP VI/Fc receptor gamma-chain-deficient but not control mice.

Conclusions

Anti-GP VI therapy may result in defective hemostasis in patients with reduced alpha2beta1 levels or concomitant aspirin therapy. These observations may have important implications for a potential use of anti-GP VI-based therapeutics in the prevention of cardiovascular disease."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.org/dc/terms/identifier"doi:10.1161/01.cir.0000146341.63677.3c"xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Nieswandt B."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Offermanns S."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Krieg T."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Eckes B."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Schulte V."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Gruner S."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Aktas B."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Moers A."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/author"Prostredna M."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/pages"2946-2951"xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/title"Anti-glycoprotein VI treatment severely compromises hemostasis in mice with reduced alpha2beta1 levels or concomitant aspirin therapy."xsd:string
http://purl.uniprot.org/citations/15505105http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/15505105http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15505105
http://purl.uniprot.org/citations/15505105http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15505105
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http://purl.uniprot.org/uniprot/#_P21279-mappedCitation-15505105http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15505105
http://purl.uniprot.org/uniprot/#_P27601-mappedCitation-15505105http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15505105
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