Enhanced Peroxisome Proliferator-Activated Receptor-γ Expression in Monocyte/Macrophages from Coronary Artery Disease Patients and Possible Gender Differences

Abstract

Peroxisome proliferator-activated receptor (PPAR) activation reduces inflammation and atherosclerosis, but recent evidence raised concerns about its beneficial clinical effects. However, the effects of gender on PPAR expression and basal cytokine release have not been investigated. In the present study, we evaluated PPAR-gamma and -alpha expression, as well as cytokine release, in monocyte/macrophages from 15 male and 15 female patients with coronary artery disease (CAD) in comparison with healthy controls. Both expression and activation of PPAR-alpha and PPAR-gamma proteins were evaluated by Western blot and electrophoretic mobility shift assay. Gene expression was evaluated by real-time polymerase chain reaction; cytokine release was measured by enzyme-linked immunosorbent assay. Monocyte/macrophages of CAD patients yielded a constitutively enhanced (approximately 10-fold; p < 0.001) protein expression of PPAR-gamma, but not PPAR-alpha, compared with healthy controls. Evaluation of PPAR-gamma gene expression showed a 60-fold increase in monocytes from CAD patients, compared with healthy donors. Moreover, monocytes spontaneously released higher amounts of proinflammatory cytokines than macrophages. It is interesting that monocytes from CAD females expressed significantly higher levels of PPAR-gamma protein compared with male patients (p < 0.05) and showed the lowest basal release of tumor necrosis factor-alpha. These results indicate that the expression of PPAR-gamma is significantly higher in CAD patients than in healthy donors and that, together with cytokine release, it seems to be gender-related. In fact, CAD women demonstrated the highest PPAR-gamma expression and the lowest cytokine release. Such differences may, in part, modulate the response to PPAR-gamma activators.