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Russian Journal |
ISSN 0042-8809 |
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Biomeditsinskaya Khimiya |
Biomedical Chemistry |
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Issue: Volume 54, issue 3
Title: VARIATIONS IN GLYCOPROTEIN IIb-IIIa (aIIb/b3-INTEGRIN) CONTENT IN HEALTHY DONORS. INFLUENCE ON
PLATELET AGGREGATION ACTIVITY AND EFFICACY OF ASPIRIN ACTION
Authors: S.G. Khaspekova1, O.V. Sirotkina2, Y.V
Shimanova1, A.V. Mazurov1.
Address:
1. Cardiology Research and Production Complex, Russian
Ministry o Health, 3rd Cherepkovskaya
15a, Moscow, 121552 Russia; fax: +7 (495) 4146735; e-mail: calab@cardio.ru;
2. Petersburg Nuclear Physics Institute, Russian
Academy of Sciences; Leningrad region, Gatchina, 188350 Russia; fax: +7 (81371)
32303; e-mail: olga_sirotkina@mail.ru.
Abstract:
Effects
of fibrinogen receptor, glycoprotein (GP) IIb-IIIa (aII/b3-integrin)
content, GP IIIa genetic polymorphism (substitution Leu33Pro) and fibrinogen
concentration in blood plasma on platelet aggregation аctivity
were studied in a group of healthy volunteers. The GP IIb-IIIa content on
platelet surface in 35 tested donors
varied (40-71)´103 per platelet. Repeated
measurements revealed that the GP IIb-IIIa content coefficient of variation was
9.5%, and deviations from mean levels did not exceed 20%. The level and rate of
platelet aggregation induced by ADP (1.25 – 20 M) correlated with GP IIb-IIIa
number (r from 0.315 to 0.591) and were higher in a group of donors with high in
comparison with low GP IIb-IIIa content (> 60 and (40-50)´103 per platelet respectively).
Aspirin, the inhibitor of thromboxane A2 synthesis, partially
suppressed ADP-induced platelet aggregation. The level of residual aggregation
in the presence of aspirin also correlated with GP IIb-IIIa content and
increased in subjects with high receptor content. Parameters of ADP-induced
aggregation did not differ in donors with GP IIIa Pro33(-) (Leu33Leu33,n = 20)
and Pro33(+) (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotype. GP IIb-IIIa
content was also not affected by GP IIIa polymorphism. No significant
correlations were found between the level and rate of platelet aggregation and
fibrinogen concentration in blood plasma. The data obtained indicate that
effects of GP IIb-IIIa variations in content on platelet aggregation are higher
than GP IIIa Leu33Pro polymorphism and
variations of fibrinogen concentration. High GP IIb-IIIa content is associated
with increased platelet aggregation activity and decreased efficacy of
aggregation inhibition by aspirin.
Key words: platelets,
glycoprotein IIb-IIIa, integrins, genetic polymorphism, fibrinogen.
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