TY - JOUR T1 - Enhanced Peroxisome Proliferator-Activated Receptor-γ Expression in Monocyte/Macrophages from Coronary Artery Disease Patients and Possible Gender Differences JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 531 LP - 538 DO - 10.1124/jpet.109.154419 VL - 331 IS - 2 AU - Angela Amoruso AU - Claudio Bardelli AU - Luigia G. Fresu AU - Alessandra Palma AU - Matteo Vidali AU - Valeria Ferrero AU - Flavio Ribichini AU - Corrado Vassanelli AU - Sandra Brunelleschi Y1 - 2009/11/01 UR - http://jpet.aspetjournals.org/content/331/2/531.abstract N2 - 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-γ and -α 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-α and PPAR-γ 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-γ, but not PPAR-α, compared with healthy controls. Evaluation of PPAR-γ 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-γ protein compared with male patients (p < 0.05) and showed the lowest basal release of tumor necrosis factor-α. These results indicate that the expression of PPAR-γ 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-γ expression and the lowest cytokine release. Such differences may, in part, modulate the response to PPAR-γ activators. © 2009 by The American Society for Pharmacology and Experimental Therapeutics ER -