Reduced neuropathy target esterase in pre‐eclampsia suppresses tube formation of HUVECs via dysregulation of phospholipid metabolism

Abstract

Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism.

DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males

“…Pnpla6 silencing significantly alters the formation of the respiratory tube and nervous system (Winrow et al, 2003 ) and impairs vasculogenesis and placental vasculature in a mouse model (Moser et al, 2004 ). PNPLA6 overexpression significantly promotes the migration and tube formation of human umbilical vein endothelial cells (HUVECs) (Li et al, 2021 ), and PNPLA6 short hairpin RNA (shRNA) inhibits the migration and tube formation of HUVECs (Li et al, 2021 ). In the current study, the results showed that the level of PNPLA6 expression was much lower in patients with IA than in the controls possibly because of the lower PNPLA6 expression in patients with IA than in the controls, consequently, the risk of angiogenic lesions increases.…”