Tobacco smoke affects expression of peroxisome proliferator-activated receptor-γ in monocyte/macrophages of patients with coronary heart disease

Background and purpose: Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPAR gamma in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPAR gamma. Here, we evaluated PPAR gamma expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPAR gamma ligands in this context. Experimental approach: PPAR gamma protein was detected by Western blot and semi-quantified by PPAR gamma/beta-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-kappa B) translocation by electrophoretic mobility shift assays. Key results: As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPAR gamma/beta-actin ratio and an increased spontaneous release of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-alpha release and NF-kappa B translocation induced by phorbol-12-myristate 13-acetate. The selective PPAR gamma antagonist GW9662 reversed these effects, with some variations related to smoking habit. Conclusions and implications: In CHD patients, exposure to tobacco smoke profoundly affected PPAR gamma expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPAR gamma expression and released more inflammatory cytokines. Moreover, rosiglitazone's ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPAR gamma involvement in these changes in CHD patients.