Unknown

Dataset Information

0

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 suppressed neovascular tuft formation. Circulating HDL-S1P activation of endothelial S1PR1 may be a key protective mechanism to guard against neovascular retinopathies that occur not only in premature infants but also in diabetes and aging.

SUBMITTER: Dr. Colin Niaudet 

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

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC10165359 | biostudies-literature
| S-EPMC3378855 | biostudies-literature
| S-EPMC5328201 | biostudies-literature
| S-EPMC7363146 | biostudies-literature
| S-EPMC6720534 | biostudies-literature
| S-EPMC7774061 | biostudies-literature
| S-EPMC9478119 | biostudies-literature
| S-EPMC5012506 | biostudies-literature
| S-EPMC7076186 | biostudies-literature
| S-EPMC5924499 | biostudies-literature