[Variations in glycoprotein IIb-IIIa (alphaIIb/beta3-integrin) content in healthy donors. Influence on platelet aggregation activity and efficacy of aspirin action].
Effects of fibrinogen receptor, glycoprotein (GP) IIb-IIIa (alphaII/(beta3-integrin) content, GP IIIa genetic polymorphism (substitution Leu33Pro) and fibrinogen concentration in blood plasma on platelet aggregation activity were studied in a group of healthy volunteers. The GP IIb-IIIa content on platelet surface in 35 tested donors varied (40-71) x 10(3) 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) x 10(3) 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.
Khaspekova
S G
SG
Sirotkina
O V
OV
Shimanova
Iu V
IuV
Mazurov
A V
AV
D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012016:Reference Values
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; D001241:Aspirin