Abstract Number: PB1021
Meeting: ISTH 2021 Congress
Background: Glycoprotein-VI (GPVI) is the major platelet collagen receptor. Two haplotypes in GPVI encoding gene (GP6) were identified previously: allele “a” – SKTQH and allele “b” – PEALN. Allele «b» carriers are more likely to suffer from cardiovascular events. These are in contradiction with Cole et al. JTH 2003 and Snoep et al. JTH 2009, who didn’t find a link between GPVI polymorphism and development of pathology. The effect of polymorphisms on platelet function (platelet aggregation, P-selectin exposure) is also controversial.
Aims: To assess the impact of GPVI polymorphisms on platelet signaling and functional responses.
Methods: 77 saliva samples were collected from healthy donors for polymorphism sequencing. Blood of the selected donors (five “aa”, five “ab”, two “bb” haplotypes) was collected by venipuncture and assessed by means of endpoint and continuous flow cytometry, fluorescent microscopy of thrombus growth, aggregometry. Computational model of platelet activation by GPVI covering platelet GPVI ligation, SFK and Syk activation, LAT-signalosome formation and calcium release from cytosolic calcium stores was constructed for data interpretation. System of ODEs was integrated using LSODA in Python 3.8.
Results: Platelet functional parameters (fibrinogen binding, alpha-granules, dense granules, procoagulant activity, thrombus coverage area, aggregation velocity, etc) were independent from polymorphism presence. Intracellular calcium level was significantly different between carriers and non-carriers of “b” allele (81±32 nM for “aa”, 33±22 nM for “ab”+ “bb”) upon platelet stimulation by 5 µg/ml of CRP. Computational model predicted these to be dependent on the variations in SFK activity, which was altered in the presence of polymorphism, according to the literature.
Conclusions: The polymorphisms of the platelet GPVI affect platelet calcium response upon stimulation, while platelet functional responses remain unaltered.
The study was supported by Russian Science Foundation (Grant 21-74-20087).
To cite this abstract in AMA style:Stepanyan M, Martyanov A, Boldova A, Filkova A, Garzon Dasgupta AK, Beresneva E, Balatsky A, Ponomarenko E, Ignatova A, Panteleev M, Sveshnikova A. Impact of the Common GPVI Polymorphism Is Limited to Intracellular Calcium Response upon Activation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/impact-of-the-common-gpvi-polymorphism-is-limited-to-intracellular-calcium-response-upon-activation/. Accessed August 16, 2022.
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