PPAR participates in both vasculogenesis and angiogenesis.

Abstract

Abstract: : Purpose: VEGF2 (KDR) plays a critical role in mediating a variety of vasculogenic and angiogenic processes. In the last ARVO meeting, we demonstrated novel findings that peroxisome proliferator–activated receptor1 (PPARγ1) increased KDR promoter activity by enhancing the interaction between Sp1, but not Sp3, and KDR promoter region without its ligand in retinal capillary endothelial cells. Conversely, PPARγ1 ligand 15–d PGJ2 suppressed the binding of KDR promoter region with both Sp1 and Sp3, resulting an inhibition of KDR gene expression. Purpose: To examine the roles of PPARγ1 in vasculogenesis and angiogenesis using PPARγ hetero KO mice<PPARγ(+/–) mice>. Methods: We first examined retinal vasucular development in both WT mice and PPARγ (+/–) mice by fluorescein–dextran perfused flat–mount preparations. We also examined the effects of PPARγ on VEGF induced angiogenesis in adult mice using Matrigel assay. Three hundred microliters of Matrigel supplemented with 100 ng VEGF with or without PPARγ ligand Pioglitazon (PIO, 20 µM) was subcutaneously inoculated into the back of the both WT mice and PPARγ (+/–) mice. The gels were embedded in paraffin, and sectioned. The sections were stained with Masson–Trichrome. Results:In WT mice, retinal vascular system developed after birth from optic disc and reached to the peripheral retina at postnatal day 7 (P7). In PPARγ (+/–) mice, retinal vascular development delayed (about 80% in diameter compared with WT mice at P7) (P<0.05). Additionally, the subcutaneous tissues attached to the Matrigel/VEGF in WT mice became reddish with fine blood vessels. While the Matrigel/VEGF in WT mice showed a clear angiogenic response with numerous vessels, the Matrigel/VEGF in PPARγ (+/–) mice showed little angiogenic response. Coadministration of PIO and VEGF resulted in the block of VEGF–induced angiogenesis in Matrigel. Conclusions: PPARγ appears to participate in both retinal vasculogenesis and VEGF–dependent angiogenesis.

Keywords: diabetic retinopathy • vascular cells • retinal development