Deletion of GIT1 Impacts eNOS Activity To Aggravate sFlt-1-Induced Preeclampsia Phenotype in Mice

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily. Urinary albumin excretion (UAE) was determined using Albuwell-M kits (Exocell Inc) and creatinine clearance (CCr) was determined by measuring urinary creatinine concentration with tandem liquid chromatography-mass spectrometry. The release of nitrite was analyzed to detect nitric oxide (NO) production using a Sievers Chemiluminescence NO Analyzer. NOS activity was examined by measuring the conversion of ³H-labeled l-arginine to ³H-labeled l-citrulline. BP was significantly increased in GIT1^-/- mice with or without sFIT-1 treatment. In addition, GIT1-/- mice possessed higher UAE and lower CCr. Depletion of GIT1 impedes the NO production and placenta eNOS activity. Additional GIT1 attenuates sFlt-1-induced preeclampsia phenotypes. Our findings suggest that GIT1 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting eNOS activity, indicating a crucial role of GIT1 in the progression of preeclampsia.