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Although a complete understanding of PE remains elusive, it has been widely accepted that a dysfunction of the placenta plays a key role in the pathogenesis of PE. In this study, we investigated the role of excessive placental autophagy during PE pathogenesis and explored whether esomeprazole ameliorates PE by inhibiting the autophagy in the placenta. The PE cellular model was established by treating the cells\u2019 L-NAME and hypoxia. The PE mice model was established by L-NAME administration and was confirmed by the increased systolic blood pressure (SBP) and urinary protein detected. The autophagy and key proteins were detected in human placental tissue, in cells, and in the mice model by Western blot and immunofluorescence staining. Results showed that excessive autophagy could be detected in human PE placental tissue, in the PE cellular model, and in the PE mice model. Hypoxia induces autophagy by activating AMPK\u03b1 and inhibiting mTOR in vivo and in vitro. Esomeprazole inhibits L\u2010NAME-induced autophagy in mice by inhibiting AMPK\u03b1 and activating mTOR. In conclusion, this study demonstrates that the excessive autophagy induced by the SIRT1\/AMPK\u03b1-mTOR pathway plays a significant role in the pathogenesis of PE. However, esomeprazole treatment inhibits AMPK\u03b1 but activates mTOR, resulting in the inhibition of autophagy in the placenta and, therefore, mitigates PE symptoms.<\/jats:p>","DOI":"10.1007\/s00441-022-03587-z","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T04:34:19Z","timestamp":1643430859000},"page":"181-194","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Esomeprazole inhibits hypoxia\/endothelial dysfunction\u2013induced autophagy in preeclampsia"],"prefix":"10.1007","volume":"388","author":[{"given":"Shengyi","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindan","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1098-5010","authenticated-orcid":false,"given":"Xiaolin","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"3587_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.metabol.2017.11.011","volume":"86","author":"C Antza","year":"2018","unstructured":"Antza C, Cifkova R, Kotsis V (2018) Hypertensive complications of pregnancy: a clinical overview. 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