Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Int J Med Sci. 2022 May 29;19(6):993-1002. doi: 10.7150/ijms.73012. eCollection 2022.
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.
子痫前期是一种严重的妊娠并发症，主要特征为滋养细胞侵袭不足、子宫螺旋动脉重塑受损、胎盘缺氧和缺血以及血管内皮功能障碍。然而，子痫前期的潜在机制仍不清楚。SIRT1 是一种 NAD+依赖的去乙酰化酶，参与多种生物学过程，包括能量代谢、氧化应激、炎症反应和细胞自噬。多项研究表明 SIRT1 可能在子痫前期的发病机制中起重要作用。本综述旨在整合 SIRT1 与子痫前期的最新研究，探讨 SIRT1 与子痫前期的综合机制。具体而言，SIRT1 可能通过自噬和衰老影响胎盘发育和滋养细胞侵袭，SIRT1 保护血管内皮细胞免受氧化应激、炎症反应、自噬和衰老的影响。此外，SIRT1 缺陷小鼠表现出典型的子痫前期样表现，可通过直接 SIRT1 补充或 SIRT1 激动剂治疗逆转。此外，SIRT1 激动剂白藜芦醇可减轻血管内皮损伤和胎盘功能障碍，降低血压，发挥保护作用。本综述为子痫前期的发展提供了新的见解，可为子痫前期的预防和治疗奠定理论基础。此外，我们还提出了一些需要进一步解决的问题，以阐明子痫前期的综合分子机制。
