Expression and activity of ectopeptidases in fibrillating human atria

Abstract

Recent studies have demonstrated that atrial fibrillation (AF) occurs in the presence of degenerative changes of atrial tissue. In contrast, bradykinin (BK) appears to have cardioprotective effects diminishing myocardial hypertrophy and fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism. Therefore, the purpose of this study was to determine the atrial expression of the membrane-bound peptidases, also referred to as ectopeptidases, carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), and alanyl-aminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or = 6 months; CAF), the remaining 18 patients (controls) had no history of AF. Peptidase expression was analyzed at the mRNA (quantitative RT-PCR) level and apparent changes were confirmed at the protein level. In case of unaltered mRNA levels, 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 controls (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 v controls: 195.8+/-21.8 pkat/mg P<0.05). APN activity was unchanged. In conclusion, atrial bradykinin metabolizing activities are significantly altered during AF in humans. The observed alterations in ectopeptidase expression/activity may play a role in the structural remodeling of fibrillating atria.