Therapeutic activation of endothelial S1PR1 suppresses proliferative retinal neovascularization

ABSTRACT: Sphingosine-1-phosphate (S1P), the circulating HDL-bound lipid mediator that acts via S1P receptors (S1PR), is required for normal vascular development. The role of this signaling axis in vascular retinopathies is unclear. Here we show in a mouse model of oxygen-induced retinopathy (OIR) that endothelial overexpression of S1pr1 suppresses while endothelial knockout of S1pr1 worsens neovascular tuft formation. Furthermore, neovascular tufts are increased in Apom-/- mice which lack HDL-bound S1P while they are suppressed in ApomTG mice which has more circulating HDL-S1P. These results suggest that circulating HDL-S1P activation of endothelial S1PR1 suppresses neovascular pathology in OIR. Additionally, systemic administration of ApoM-Fc-bound S1P or a small molecule Gi-biased S1PR1 agonist s

SUBMITTER: Dr. Colin Niaudet 

PROVIDER: S-SCDT-10_15252-EMMM_202216645 | biostudies-other |

REPOSITORIES: biostudies-other