Gender and age-dependent differences in the bradykinin-degradation within the pericardial fluid of patients with coronary artery disease

Cardiovascular diseases (CVD) and, in particular, coronary artery disease (CAD) are the leading causes of death in developed countries, especially in the elderly population. Males exhibit a higher risk for cardiovascular events than women. The pericardial fluid (PF) is in direct contact with the epicardial sections of the coronary arteries and the perimyocardium. A systematic analysis of gender-specific or age-related differences in angiotensin-related pathways like bradykinin metabolism however, has not been performed in the PF so far. Therefore, the amounts of angiotensin-converting enzyme (ACE) and the rate of the degradation of bradykinin (BK) and the amounts/activity of major BK-degrading enzymes, aminopeptidase N (APN) and dipeptidyl-aminopeptidase IV (DPIV), were assessed in the pericardial fluid (PF) of 44 patients undergoing coronary artery bypass grafting. We found BK being degraded within the PF. Interestingly, there was an age-dependent decrease in the amounts of ACE protein in women. In elderly women, ACE/APN and ACE/DPIV ratios were substantially reduced to 41.4% or 29.4% respectively (p<0.05). In contrast, an age-dependent decline of ACE protein and ACE/protease ratios were not found in men. In men and women, total BK degradation correlated with age (r=0.5; p=0.021) further supporting a switch in BK metabolising enzymes in elderly women. Thus, we can show age-and gender-dependent differences in BK metabolism within the PF in patients with coronary artery disease. The present finding that the expression of ACE is lowest in elderly women, despite the presence of similar BK degradation, might help to explain the potentially reduced therapeutic effects of ACE inhibitors in elderly women. (C) 2009 Elsevier Ireland Ltd. All rights reserved.