Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina

Abstract

Abstract. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is able to induce the expression of vascular endothelial growth factor (VEGF), promoting the formation of new blood vessels in skeletal muscle. The aim of the current study was to determine whether PGC-1α is able to regulate angiogenesis in human retinal vascular endothelial cells (hRVECs) in vitro and in retinas in vivo. hRVECs treated with recombinant PGC-1α were incubated for 24 h and then placed into a normoxic (20% O 2 ) or hypoxic (1% O 2 ) environment for a further 16 h. Following this, VEGF mRNA and protein levels were significantly increased. Cellular proliferation was enhanced by treatment with recombinant PGC-1α in normoxic and hypoxic conditions. At 24 h following recombinant PGC-1α treatment, hRVECs were plated into Matrigel-coated plates and cultured under normoxic (20% O 2 ) or hypoxic (1% O 2 ) conditions for a further 24 h. Recombinant PGC-1α-treated cells were observed to form significantly greater numbers of tubes. In a C57BL/6J mouse model of ischemic retinopathy, mice received an intravitreal injection of recombinant PGC-1α, resulting in a significant increase in VEGF mRNA and protein levels in the retina. Retinal neovascular tufts and neovascular nuclei were investigated by angiographic and cross-sectional analysis and were observed to be significantly increased in the PGC-1α group compared with the control group. These results indicate that PGC-1α is able to induce angiogenesis in hRVECs and retinas, and suggests that PGC-1α is a potential anti-angiogenic target in retinal neovascularization.

PPARs and Angiogenesis—Implications in Pathology

“…Also 15-lipoxygenase-1 gene transfer decreased pathological retinal angiogenesis in a comparable model via PPARγ and down-regulation of Vegfr-2 [ 113 ]. In a mouse model of ischemic retinopathy, animals receiving an intravitreal injection of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) showed increased VEGF levels in the retina and enhanced angiogenesis [ 114 ]. Whether this intravitreal injection of a normally nuclear expressed PPAR co-activator is relevant for retinal pathologies is questionable.…”