Abstract: SA-PO1073

Impairment of Key Sphingolipid Metabolism Enzymes in Placenta and Kidneys of Reduced Uterine Perfusion Mouse Model

Session Information

Category: Hypertension

  • 1101 Hypertension: Basic and Experimental - Neural and Inflammatory Mechanisms

Author

  • Intapad, Suttira, Tulane University School of Medicine, New Orleans, Louisiana, United States
Background

Preeclampsia (PE), is a pregnancy disorder characterized in the early gestation by placental ischemia, hypertension, and proteinuria. These complications may lead to the development of chronic kidney disease. Bioactive sphingolipids ceramide and sphingosine-1-phosphate (S1P) function as key regulators of cellular homeostasis such as angiogenesis, inflammation and endothelial permeability. Ceramide and S1P levels are altered in preeclamptic women, and sphingolipid pathway has been reported to involve in renal injury. Ceramidase hydrolyzes ceramide to produce sphingosine. Sphingosine can then be phosphorylated by sphingosine kinase (Sphk) 1 and 2 to form S1P. In the present study, we tested the hypothesis that placental ischemia alters the acid ceramidase 1 (ASAH1), Sphk1 and Sphk2 enzymes expression in placenta and kidneys of reduced uterine perfusion (RUP) mouse model.

Methods

C57bl/6J mice underwent sham or RUP surgeries at day 13 of gestation. Mice were instrumented with a carotid arterial catheter for measurement of mean arterial pressure (MAP) at E18 in the conscious state. Placenta and kidneys were harvested after MAP measurement and subjected to western blot analysis.

Results

MAP was significantly elevated in RUP (N=8) versus sham (N=5) (122±2 vs. 105±3 mmHg, P<0.01; respectively). ASAH1 were significantly(P<0.01) lower in the kidneys (50%) and placenta (40%) of RUP (N=4) compared to sham (N=4) . Sphk 1 and Sphk 2 were significantly decreased in the placenta of RUP compared to sham (30 % decrease in Sphk1 and 55 % decrease in Sphk2). However, Sphk1 and sphk2 were significantly increased in kidneys of RUP (N=4) compared to sham (N=4) (100 % increase in Sphk1 and 75 % increase in Sphk2).

Conclusion

Taken together, this study suggests the reduced uterine perfusion in mice alters keys sphingolipid metabolism enzymes in placenta and kidneys and may play an important role in the pathogenesis of PE.

Funding

  • Private Foundation Support