{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:45:07Z","timestamp":1778600707428,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scott, Sherwood and Brindley Foundation"},{"name":"Department of Obstetrics and Gynecology (MNU)"},{"name":"Noble Centennial Endowment for Research in Obstetrics and Gynecology"},{"name":"Baylor Scott &amp; White Healthcare, Temple, Texas"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>There are no effective therapies to prevent preeclampsia (PE). Pravastatin shows promise by attenuating processes associated with PE such as decreased cytotrophoblast (CTB) migration, aberrant angiogenesis, and increased oxidative stress. This study assesses the effects of pravastatin on hyperglycemia-induced CTB dysfunction. Methods: Human CTB cells were treated with 100, 150, 200, 300, or 400 mg\/dL glucose for 48 h. Some cells were pretreated with pravastatin (1 \u00b5g\/mL), while others were cotreated with pravastatin and glucose. The expression of urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) mRNA, vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) were measured. CTB migration was assayed using a CytoSelect migration assay kit. Statistical comparisons were performed using an analysis of variance with Duncan\u2019s post hoc test. Results: The hyperglycemia-induced downregulation of uPA was attenuated in CTB cells pretreated with pravastatin at glucose levels &gt; 200 mg\/dL and cotreated at glucose levels &gt; 300 mg\/dL (p &lt; 0.05). Hyperglycemia-induced decreases in VEGF and PlGF and increases in sEng and sFlt-1 were attenuated in both the pretreatment and cotreatment samples regardless of glucose dose (p &lt; 0.05). Pravastatin attenuated hyperglycemia-induced dysfunction of CTB migration. Conclusions: Pravastatin mitigates stress signaling responses in hyperglycemic conditions, weakening processes leading to abnormal CTB migration and invasion associated with PE in pregnancy.<\/jats:p>","DOI":"10.3390\/cells13181534","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T03:03:37Z","timestamp":1726196617000},"page":"1534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pravastatin Protects Cytotrophoblasts from Hyperglycemia-Induced Preeclampsia Phenotype"],"prefix":"10.3390","volume":"13","author":[{"given":"Ahmed F.","family":"Pantho","sequence":"first","affiliation":[{"name":"Artemis Biotechnologies LLC, Temple, TX 76504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Baylor Scott & White Health, Temple, TX 76508, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janhavi V.","family":"Govande","sequence":"additional","affiliation":[{"name":"University of Texas Medical School at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riddhi","family":"Rane","sequence":"additional","affiliation":[{"name":"Texas A&M University College of Medicine, College Station, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-9895","authenticated-orcid":false,"given":"Niraj","family":"Vora","sequence":"additional","affiliation":[{"name":"Baylor Scott & White Health, Temple, TX 76508, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey R.","family":"Kelso","sequence":"additional","affiliation":[{"name":"Baylor Scott & White Health, Temple, TX 76508, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Kuehl","sequence":"additional","affiliation":[{"name":"Artemis Biotechnologies LLC, Temple, TX 76504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven R.","family":"Lindheim","sequence":"additional","affiliation":[{"name":"Baylor Scott & White Health, Temple, TX 76508, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-7805","authenticated-orcid":false,"given":"Mohammad N.","family":"Uddin","sequence":"additional","affiliation":[{"name":"Artemis Biotechnologies LLC, Temple, TX 76504, USA"},{"name":"Baylor Scott & White Health, Temple, TX 76508, USA"},{"name":"Texas A&M University College of Medicine, College Station, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1016\/j.placenta.2011.11.021","article-title":"Review: Biochemical markers to predict preeclampsia","volume":"33","author":"Anderson","year":"2012","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1097\/00006254-200209000-00023","article-title":"Preeclampsia. 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