Estrogen Influences Human Microvascular Endothelial Function Via Sex-Specific Regulation of Sphingolipids

Microvascular endothelial dysfunction strongly predicts poor cardiovascular outcomes, and recent studies have indicated that chronic estrogen treatment promotes endothelial dysfunction in isolated human microvessels. Here, using a translational approach, we demonstrate that sphingolipids are a critical component of estrogen signaling within the human microvascular endothelium. We provide evidence that the stark differences in how estrogen influences the microvascular endothelium are both time- and sex-dependent. This work adds mechanistic insight regarding the complexity and often contradictory relationship between estrogen and cardiovascular risk in humans.