SIRT1: A Novel Protective Molecule in Pre-eclampsia

Int J Med Sci. 2022 May 29;19(6):993-1002. doi: 10.7150/ijms.73012. eCollection 2022.

Abstract

Pre-eclampsia is a severe pregnant complication, mainly characterized by insufficient trophoblast invasion, impaired uterine spiral artery remodeling, placental hypoxia and ischemia, and endothelial dysfunction. However, the potential mechanisms of pre-eclampsia remain unclear. SIRT1 is a NAD+-dependent deacetylase, involving in multiple biological processes, including energy metabolism, oxidative stress, inflammatory response, and cellular autophagy. Several studies showed that SIRT1 might play a vital role in the pathogenesis of pre-eclampsia. In this review, we aim to integrate the latest research on SIRT1 and pre-eclampsia to explore the comprehensive mechanisms of SIRT1 in pre-eclampsia. More specifically, SIRT1 might affect placental development and trophoblast invasion through autophagy and senescence in pre-eclampsia, and SIRT1 protects vascular endothelial cells from oxidative stress, inflammatory response, autophagy, and senescence. Furthermore, SIRT1 deficiency mice showed typical pre-eclampsia-like performances, which can be reversed via direct SIRT1 supplement or SIRT1 agonist treatment. Additionally, resveratrol, a SIRT1 agonist, attenuates vascular endothelial injury and placental dysfunction, and exerts protective effect on decreasing blood pressure. In this review, we provide new insights into the development of pre-eclampsia, which can establish a theoretical basis for prevention and treatment for pre-eclampsia. Besides, we also propose questions that still need to be further addressed in order to elucidate the comprehensive molecular mechanisms of pre-eclampsia in the future.

Keywords: SIRT1; endothelial cells (ECs); pre-eclampsia (PE); resveratrol; trophoblasts.

Publication types

  • Review

MeSH terms

  • Animals
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Placenta / metabolism
  • Pre-Eclampsia* / drug therapy
  • Pregnancy
  • Sirtuin 1 / metabolism
  • Trophoblasts

Substances

  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1