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Abstract: Objective: Activation of peroxisome proliferator-activated receptor α (PPARα) and PPARγ plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARα and γ have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARδ remains poorly studied. Methods and results: We focused on PPARδ function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARδ is the predominantly expressed isotype whereas PPARα was weakly detected. By performing cell viability assays, we also showed that the selective PPARδ agonist GW501516 protected cells from H2O2-induced cell death. The protective effect of GW501516 was due to an inhibition of H2O2-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARδ that the protection induced by GW501516 was totally dependent on PPARδ. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H2O2-triggered apoptosis, as evidenced by annexin-V labeling. Conclusion: Taken together, our results account for an important role of PPARδ in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARδ appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences. [Copyright &y& Elsevier]

Objectives: To study the influence of pregnancy and labor on the proportion and level of activation of monocyte subpopulations in human pregnancy. Study Design: Peripheral blood samples were obtained from healthy nonpregnant women (n = 6); women in the third-trimester of healthy pregnancies (n = 18) and women with preterm premature rupture of membranes (n = 46), just before delivery for the last 2 groups. Monocyte subpopulations were characterized by flow cytometry using CD14, CD16, and activation level using macrophage chemoattractant protein-1 (MCP-1) and CCR2 antibodies. Results: The relative proportion of each monocyte subset in nonpregnant women was similar to that in women with healthy or complicated pregnancies. However, pregnancy was associated with a significant decrease in MCP-1 expressing monocytes (79.5% ± 19.8% vs 9.3% ± 6.8% and 11.9% ± 8.3% for nonpregnant, healthy pregnancy, and preterm premature rupture of membranes (respectively, P < .05). Spontaneous labor was associated with a return to nonpregnant values for the proportion of MCP-1 expressing monocytes in both normal (74.4% ± 16.9) and preterm premature rupture of membranes pregnancy (68.4% ± 35.6), irrespective of the mode of delivery (vaginal or cesarean section). This was not observed in women who delivered without spontaneous labor onset. CCR-2 (MCP-1 receptor) expression was not modified in monocytes at the time of labor, but was significantly increased in granulocytes (3646 ± 1080 vs 7338 ± 2718 for nonlaboring and laboring preterm premature rupture of membranes, respectively, P < .05) Conclusion: In light of previous reports of a role for MCP-1 in labor, our results suggest the downregulation of activation levels of monocytes, via MCP-1 expression might be involved in maternofetal immune tolerance. Monocyte reactivation might be associated with labor. [ABSTRACT FROM AUTHOR]