Peroxisome proliferator-activated receptor. mediates porcine placental angiogenesis through hypoxia inducible factor-, vascular endothelial growth factor- and angiopoietin-mediated signaling

Peroxisome proliferator-activated receptor (PPAR). has been reported to be implicated in placentation in mice. Previous studies have demonstrated that PPAR gamma is also expressed in porcine placenta, primarily localized in vascular endothelial cells (VECs). The present study aimed to investigate the roles of PPAR gamma during porcine placental angiogenesis and examine the molecular mechanisms involved in its actions. VECs were incubated with the PPAR gamma agonist rosiglitazone and the antagonist T0070907, and their angiogenic potential was evaluated using cellular impedance, wound healing and tube formation assays. Reverse transcription-quantitative polymerase chain reaction was used to assess the mRNA expression levels of angiogenic factors, including hypoxia-inducible factors (HIFs), vascular endothelial growth factor (VEGF) isoforms, VEGF receptors (VEGFRs) and angiopoietins (Angs). The results demonstrated that the adhesive, proliferative and migratory capabilities of VECs were potentiated by rosiglitazone and suppressed by T0070907. Notably, tube formation was invariably promoted during PPAR gamma activation and blockade. The mRNA expression levels of HIF1a, HIF2a, VEGFR2, VEGF188 and Ang-1 were revealed to be upregulated following treatment of VECs with rosiglitazone, whereas they were downregulated following treatment with T0070907. However, the mRNA expression levels of placental growth factor and VEGF120 were consistently downregulated following PPAR gamma activation and blockade, whereas VEGF164 mRNA levels remained unaltered. The results of the present study suggested that PPAR gamma may mediate porcine placental angiogenesis, by interfering with HIF-, VEGF-and angiopoietin-mediated signaling pathways.