Abstract
Pre-eclampsia is a severe hypertensive disorder of pregnancy (HDP), mainly characterized by new-onset hypertension with proteinuria after 20-week gestation. Sirtuin1 (SIRT1), a class III histone deacetylase, is associated with the regulation of various pathophysiological processes, including inflammation, immune response, metabolism, and autophagy. However, the effect of SIRT1 in the pathogenesis of pre-eclampsia remains to be elucidated. In this study, we found that the expression of SIRT1 was relatively lower in the placentas and serum samples of pre-eclampsia patients. Typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, fetal growth restriction, kidney injury, and a narrow placental labyrinth layer, were observed in SIRT1 knockdown (SIRT1+/−) mice. Of note, these performances could be improved after the intraperitoneal injection of SIRT1 agonist SRT2104. More importantly, we found that the efficacy of progesterone on attenuating symptoms of PE was profoundly better than that of metformin in SIRT1+/− mice. In addition, our results suggested that progesterone can promote the invasion and inhibit the apoptosis of trophoblasts. These data suggest that SIRT1 plays an important role in pre-eclampsia and that progesterone alleviates pre-eclampsia-like symptoms mediated by SIRT1 deficiency.
Highlights
To study the role of SIRT1 in PE, we evaluated the level of SIRT1 expression in human placental tissues from women with pre-eclampsia with severe features (n = 7) and normal pregnant women (NP) (n = 7) (Figure 1)
We found that the expression of SIRT1 was significantly lower in placentas and serum samples of pre-eclampsia patients
Showed typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, fetal mice showed typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, growth restriction, kidney injury, and a narrowed placental labyrinth layer, implying that fetal growth restriction, kidney injury, and a narrowed placental labyrinth layer, implying thethat construction of the PE-like model was successful, and SIRT1and heterozygote knockthe construction of themice
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Pre-eclampsia (PE) is defined as new-onset hypertension with proteinuria after 20-week gestation. In severe cases, it can combine with renal, cardiac, pulmonary, hepatic, and neurological dysfunction; hematologic disturbances; fetal growth restriction; stillbirth; and even maternal death [1]. Pre-eclampsia impacts 2 to 8% of all pregnancies worldwide, which is a major cause of maternal and fetal morbidity and mortality, and the only known cure for this complication is delivery [2,3]. Elucidating the pathophysiological mechanisms of pre-eclampsia will help us accurately prevent, manage, and treat it to avoid maternal and fetal losses
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