Aspirin alters the cardioprotective effects of the factor XIII Val34Leu polymorphism

Article

关键词: MICROVASCULAR INJURY;    ACTIVATION;    THROMBIN;    FIBRINOGEN;    BLOOD;    COAGULATION;    GENERATION;    SITE;   

DOI  :  10.1161/01.CIR.0000047062.03282.A3

来源: SCIE

【 摘 要 】

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 Va134Leu polymorphism on its activation in vivo. Methods and 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 Va134 hotnozygotes 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 Va134 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.

【 授权许可】

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