One of the more common factors contributing to heart failure is progressive atherosclerosis or coronary arterial disease (CAD). A significant process that contributes to CAD is the activation of inflammatory monocytes and macrophages. The resulting inflammation contributes to further elaboration of atherosclerotic plaques and collateral damage that increase the chance for development of heart failure. Because women are less likely to progress to heart failure, there is the possibility that the gender difference is due to differences in inflammatory responses. In this issue, Amoruso et al., examine possible gender differences in activation of inflammatory cells found in CAD patients. Specifically, the study examines expression of the peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ in monocytes and macrophages from patients with CAD. The PPAR-α and PPAR-γ nuclear receptors mediate expression of genes that suppress inflammatory cytokine expression and secretion. The authors found that PPAR-γ mRNA and protein expression levels were significantly higher in patients with CAD than in healthy controls. They also observed that PPAR-γ expression levels were much higher in female patients with CAD than in male patients. In addition, monocytes from female patients with CAD release less of the master regulator cytokine tumor necrosis factor-α than do cells from male subjects with CAD. Given that the thiazolidinedione class of selective PPAR-γ agonists is used for insulin sensitization in patients with diabetes, many of whom also suffer from CAD, the observation of gender differences has direct clinical relevance.
See article at J Pharmacol Exp Ther 2009, 331:531–538.
- © 2009 by the American Society for Pharmacology and Experimental Therapeutics