Measurement of Platelet Collagen Receptor Density in Human Subjects

Samaha, Frederick F.; Hibbard, Christopher; Sacks, Jay; Chen, Hong; Varello, Michael; George, Thomas; Kahn, Mark L.

doi:10.1161/01.atv.0000144809.49724.71

Cited by 12 publications

(8 citation statements)

References 20 publications

(23 reference statements)

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“…21 The influence of N-glycosylation on GPVI function potentially represents another basis for heterogeneity of this receptor and may contribute to the range of expression and/or activity seen between individuals, as reported by our group 11 and others. 22,23 Moreover, abnormalities in N-glycosylation of GPVI could contribute to acquired defects in GPVI-mediated platelet reactivity to collagen, such as recently reported in 2 patients with malignant hemopathies. 24 …”

Section: Discussionmentioning

confidence: 92%

The influence of N-linked glycosylation on the function of platelet glycoprotein VI

Kunicki

Chéli

Moroi

et al. 2005

Blood

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Section: Discussionmentioning

confidence: 92%

The influence of N-linked glycosylation on the function of platelet glycoprotein VI

Kunicki

Chéli

Moroi

et al. 2005

Blood

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“…Normal GPVI levels have been shown to be either tightly regulated, varying by only 1·5‐fold (Best et al , 2003), or up to fivefold (Furihata et al , 2001). In a group of outpatients, GPVI levels varied by 16‐fold (Samaha et al , 2004). These discrepancies could reflect the different methods used for measuring GPVI – semi‐quantitative ligand blot assays using biotinylated convulxin (Furihata et al , 2001) versus flow cytometry using GPVI monoclonal antibodies in the other studies.…”

Section: Gpvi Expression Levels and Diseasementioning

confidence: 99%

Platelet glycoprotein VI‐related clinical defects

2007

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SummaryHuman patients with defects associated with the platelet collagen receptor, glycoprotein (GP)VI, are rare and usually described as having a mild bleeding disorder. However, here we review clinical profiles of patients with familial or acquired GPVI defects, revealing the bleeding defect is often severe and associated with immune dysfunction. GPVI is a member of the immunoreceptor family, and co-expressed on platelets with Fc receptor c-chain (FcRc). Ligand binding to GPVI leads to activation of platelet integrins, in particular a IIb b 3 that mediates platelet aggregation; and activation of endogenous platelet metalloproteinases resulting in ectodomain shedding and release of a soluble GPVI fragment. Increasing evidence supports the functional importance of GPVI/FcRc in thrombus formation at arterial shear rates, and expression levels of platelet GPVI may be a marker of thrombotic risk. Over the past 20 years, patients have been reported with GPVI-related defects involving: (i) an acquired deficiency, resulting from (a) anti-GPVI autoantibodies or (b) other causes; or (ii) a congenital deficiency, where (c) GPVI is not expressed or (d) is expressed in a dysfunctional form with defective signalling to a IIb b 3 . Clinical consequences of GPVI-related defects may be uniquely informative about the role of platelet GPVI in health and disease.

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“…32 Being different from other types of glycoproteins, GP Ia/IIa density varies by up to 10-fold among normal individuals, which is considered to be caused by genetic variations. [33][34][35] Moreover, platelet attachment to type I collagen at high shear stress in whole blood is more extensive in patients with high GPIa/IIa density. 36 The effect of the extreme case was illustrated in a patient who totally failed to express platelet GPIa, and this patient exhibited complete absence of collageninduced aggregation and an excessively prolonged bleeding time.…”

Section: Discussionmentioning

confidence: 99%

Common Variant in Glycoprotein Ia Increases Long‐Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery

Liu

et al. 2016

JAHA

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BackgroundThis study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms.Methods and ResultsWe genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T‐allele carriers have a higher major adverse cardiac or cerebrovascular events risk post‐CABG than those who are CC homozygotes (hazard ratio [HR]=1.29; P=0.022). The clinical association between the risk allele (T) carriage and major adverse cardiac or cerebrovascular events was confirmed in another cohort study, which included 646 CABG patients from various health centers across China. Meanwhile, rs1126643 T allele was also linked with increased risk of major adverse cardiac or cerebrovascular events (HR=1.73; P=0.019). To explore the underlying mechanisms, we prospectively recruited 131 coronary artery disease patients, assessed their platelet aggregation function, and focused on detecting their GPIA mRNA level and protein expression. Results showed that patients with rs1126643 T allele have elevated platelet aggregation activity (P=0.029) when protein expression is increased (P<0.001) and not affected by glycoprotein Ia mRNA level.ConclusionsThe synonymous common variant, GPIA rs1126643, increases the long‐term adverse events risk of CABG by augmenting GPIa protein expression and enhancing platelet aggregation function. This finding can serve as the implication of improving secondary prevention of CABG patients.

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Measurement of Platelet Collagen Receptor Density in Human Subjects

Cited by 12 publications

References 20 publications

The influence of N-linked glycosylation on the function of platelet glycoprotein VI

The influence of N-linked glycosylation on the function of platelet glycoprotein VI

Platelet glycoprotein VI‐related clinical defects

Common Variant in Glycoprotein Ia Increases Long‐Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery

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