Umbilical cord plasma-derived exosomes from preeclamptic women induce vascular dysfunction by targeting HMGCS1 in...

Hypertension is one of the major clinical manifestations of preeclampsia. Vascular dysfunction is crucial for the occurrence and progression of hypertension. Exosomes are emerging as mediators of intercellular communication and can participate in angiogenesis. In this study, we hypothesize that umbilical cord plasma-derived exosomes from preeclamptic women (PE-uexo) impair vascular development by regulating endothelial cells. Here, umbilical cord plasma samples from women with normal pregnancies and matched preeclamptic patients were used to isolate circulating exosomes. Proliferation, Transwell and tube formation assays indicated that PE-uexo impaired the angiogenesis of human umbilical vein endothelial cells (HUVECs). On the basis of microarray analysis of HUVECs treated with PE-uexo or exosomes from women with normal pregnancies, we showed that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) was decreased in the PE-uexo-treated HUVECs. Furthermore, downregulation of HMGCS1 in HUVECs attenuated the proliferation and migration of these cells. Interestingly, HMGCS1 was decreased in P0 HUVECs from preeclamptic pregnancies compared with normotensive pregnancies. Together, these observations suggest that PE-uexo disrupts normal function in vascular endothelial cells by targeting HMGCS1, which may result in vascular disorders in the offspring.