Aspirin alters the cardioprotective effects of the factor XIII Val34Leu polymorphism.
BACKGROUND
The mechanism underlying decreased risk for myocardial infarction in carriers of the Leu34 polymorphism of the factor (F) XIII A-subunit is unclear. Given that acetylation of fibrinogen by aspirin can alter its clotting properties and the presence of fibrin stimulates thrombin-mediated activation of FXIII, we have tested the hypothesis that treatment with aspirin differentially modulates the influence of the FXIII Val34Leu polymorphism on its activation in vivo.


RESULTS
The rates of the disappearance of FXIIIA chain and the appearance of its activated form (FXIIIAa) in sequential 30-second blood samples collected at the site of microvascular injury were compared in 14 healthy carriers of the Leu34 allele and 23 Val34 homozygotes both before and after a 7-day aspirin ingestion (75 mg/d), with the use of quantitative Western blotting. The presence of the Leu34 allele was associated with a significant increase in the maximum rate of FXIII activation by thrombin. Although the Leu34-positive and -negative subjects were similar with respect to aspirin-related impairment of thrombin generation, aspirin led to a more pronounced inhibition of the activation of FXIII in the Leu34 carriers as compared with the Val34 homozygotes.


CONCLUSIONS
Inhibition of FXIII activation by aspirin is enhanced in the Leu34 carriers in vivo, suggesting that these subjects might benefit more than the Leu34-negative subjects from the reduction in risk for myocardial infarction with low-dose aspirin.
Undas
Anetta
A
Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
Sydor
Wojciech J
WJ
Brummel
Kathleen
K
Musial
Jacek
J
Mann
Kenneth G
KG
Szczeklik
Andrew
A
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000032:analysis / Q000037:antagonists & inhibitors; D005176:Factor XIII / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D026122:Factor XIIIa / Q000032:analysis; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control; D020641:Polymorphism, Single Nucleotide
D002316:Cardiotonic Agents; D005176:Factor XIII; D026122:Factor XIIIa; D001241:Aspirin