Abstract 105: Mitotempol Restores Endothelial Dysfunction In Placental Arterioles In Preeclampsia

Abstract

Preeclampsia (PreE) is complication of pregnancy, affecting 5% of pregnancies in the United States, and presenting a significant burden to our healthcare systems. Oxidative damage and dysfunction of the placental microcirculation has been implicated. Clinical trials of antioxidant therapies to treat PreE have failed. However, none of these studies have used targeted antioxidants. Given that vascular compromise in preeclampsia may be caused by mitochondrial dysfunction, we propose that MitoTEMPOL (MT), a mitochondrial-targeted superoxide dismutase mimetic, will restore endothelium-dependent vasodilation in human placental arterioles. Arterioles from the maternal portion of the placenta of average diameter 161.1 ± 11.1 μm were cannulated on glass micropipettes and constricted with 0.1-1.5 nM endothelin-1 and flow was generated with a pressure gradient across vessel reservoirs. Flow-mediated dilation (FMD) was measured by video-microscopy presented as % maximal diameter from baseline. Smooth muscle function was evaluated by exposure to 100 μM papaverine. Vessels from normal placentas dilated to flow by 70.2% ± 3.8% (n=11), whereas vessels from PreE placentas dilated to only 47.9% ± 5.6% (n=8, p=0.005). Exposure to 10 μM of MT for 30 minutes in the organ bath restored Pre-E vessel dilation to 80.0% ± 3.9% (n=6, p=0.0003 vs PreE). FMD in normal vessels was not affected by exposure to MT (75.9% ± 7.2%, n=4, p=0.84). Significance was evaluated by 2-way ANOVA, α = 0.05. MT restores endothelium-dependent vasodilation in PreE vessels. Further evaluation of other mitochondrial-targeted antioxidants could lead to novel therapeutic options to improve vascular function in PreE.