{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:37Z","timestamp":1787027497530,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Massachusetts Life Science Center (MLSC) USA\u2013Women\u2019s Health Innovation Grant","award":["2021\u20132023"],"award-info":[{"award-number":["2021\u20132023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5\u20137% of patients. There is no effective treatment available. Early abnormal placental development is associated with oxidative stress (OS) and a release of reactive oxygen species (ROS) in the placenta. This phenomenon leads to downstream signaling, Hypoxia Inducible Factor 1A (HIF1A) stabilization and transcription of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sEng), which are known to cause endothelial and trophoblast dysfunction and cardinal features of PE: hypertension, proteinuria and, in severe cases, eclampsia. We tested whether 3-(Hydroxymethyl)-1-oxy-2,2,5,5-tetramethylpyrrolidine (HMP)\u2014a nitroxide-type antioxidant molecule\u2014can reduce placental OS and mitigate PE symptoms in vitro. We induced OS in human trophoblast (HTR-8\/SVneo) cells with hydrogen peroxide (H2O2) and assessed whether modulating cell redox function with HMP reduces cell injury, mitochondrial stress and HIF1A and sFLT1 production. Pre-treatment with HMP reduced mitochondrial-derived ROS production, restored LC3B expression and reduced HIF1A and sFLT1 expression in H2O2-exposed HTR-8\/SVneo trophoblast cells. HMP improved the mitochondrial electron chain enzyme activity, indicating that a reduction in OS alleviates mitochondrial stress and also reduces anti-angiogenic responses. In reducing placental trophoblast OS, HMP presents a potential novel therapeutic approach for the treatment of PE. Future investigation is warranted regarding the in vivo use of HMP.<\/jats:p>","DOI":"10.3390\/antiox12081578","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:35:42Z","timestamp":1691498142000},"page":"1578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nitroxide\u2014HMP\u2014Protects Human Trophoblast HTR-8\/SVneo Cells from H2O2-Induced Oxidative Stress by Reducing the HIF1A Signaling Pathway"],"prefix":"10.3390","volume":"12","author":[{"given":"Diana","family":"Pintye","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-4331","authenticated-orcid":false,"given":"R\u00e9ka Eszter","family":"Sziva","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Obstetrics and Gynecology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Mastyugin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts, Boston, MA 02125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts, Boston, MA 02125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonako","family":"Jacas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira","family":"Salahuddin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-5728","authenticated-orcid":false,"given":"Zsuzsanna K.","family":"Zsengell\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","unstructured":"American College of Obstetricians and Gynecologists (2013). 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