Expression and activity of ectopeptidases in fibrillating human atria

Recent studies have demonstrated that atrial fibrillation (AF) occurs in th e presence of degenerative changes of atrial tissue. In contrast, bradykini n (BK) appears to have cardioprotective effects diminishing myocardial hype rtrophy and fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism. Therefore, the purpose of this study was to determine th e atrial expression of the membrane-bound peptidases, also referred to as e ctopeptidases, carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), an d alanylaminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35 patients undergoing open heart surgery were examined. Sevent een patients had chronic persistent AF (greater than or equal to6 months; C AP), the remaining IS patients (controls) had no history of AF. Peptidase e xpression was analyzed at the mRNA (quantitative RT-PCR) level and apparent changes were confirmed at the protein level. In case of unaltered mRNA lev els, enzyme activity was determined. Reduced amounts of CPM-mRNA were found in patients with CAF (41.3 +/-9.7 U nu controls: 86.1 +/- 17.5 U; P<0.05). CPM protein was decreased to 47.5% in patients with CAF compared with cont rols (P<0.01). DPIV and APN mRNA amounts were similar in both groups. DPIV activity, however, was increased during CAF (219.6 +/- 30 pkat/mg protein n u controls: 195.8 +/- 21.8 pkat/mg; P<0.05). APN activity was unchanged. In conclusion, atrial bradykinin metabolizing activities are significantly al tered during AF in humans. The observed alterations in ectopeptidase expres sion/activity may play a role in the structural remodeling of fibrillating atria. (C) 2001 Academic Press.