Proteolytic and genetic variation of the alpha-2-antiplasmin C-terminus in myocardial infarction.

摘要

Alpha-2-antiplasmin (alpha2AP) undergoes both N- and C-terminal cleavages, which significantly modify its activities. Compared with other Ser protease inhibitors (serpins), alpha2AP contains an ~50-residue-extended C-terminus, which binds plasmin(ogen). We developed 2 new ELISAs to measure the antigen levels of free total alpha2AP and free C-terminally intact alpha2AP to investigate whether alpha2AP antigen levels or alpha2AP C-terminal cleavage were associated with myocardial infarction (MI) in 320 male MI survivors and 169 age-matched controls. Patients had 15.2% reduced total alpha2AP antigen levels compared with controls (93.8 vs 110.6 U/dL, P < .001), with a 10.1-fold (95% confidence interval [CI]: 5.5-18.9) increased MI risk for levels in the 1st quartile compared with the 4th quartile. The percentage of C-terminal cleavage did not differ between patients and controls (38.7% and 38.1%, respectively, P = .44). In addition, all individuals were genotyped for the polymorphism Arg407Lys, which is located near the start of the extended C-terminus. Arg407Lys was not associated with alpha2AP C-terminal cleavage, total alpha2AP antigen levels, or MI risk (odds ratios compared with Arg/Arg: Arg/Lys 0.74, 95% CI: 0.50-1.10; Lys/Lys 0.77, 95% CI: 0.31-1.92). Our data show that levels of free full-length alpha2AP were decreased in MI, that the percentage of C-terminally cleaved alpha2AP was unaltered, and that Arg407Lys did not influence alpha2AP levels or MI risk.