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The hemodynamic mechanisms underlying statin protection in OAPS remain unclear. In this study, the therapeutic potential of simvastatin in OAPS was investigated. Herein, an OAPS mouse model was used to evaluate the effects of simvastatin on pregnancy outcomes and uteromaternal hemodynamics. A placenta\u2010on\u2010a\u2010chip platform was engineered to assess trophoblast invasion under high shear stress. Transcriptome sequencing and molecular assays validated the mechanisms by which simvastatin mitigates endothelial injury induced by antiphospholipid antibodies. Simvastatin attenuated maternal vascular inflammation and rectified uteromaternal hemodynamic aberrations in mice. Furthermore, treatment indirectly promoted trophoblast invasion under high shear stress, facilitating spiral artery remodeling and improving placental perfusion. Mechanistically, these effects were mediated by activation of the endothelial Kruppel\u2010like factor 2 (KLF2)\/endothelial nitric oxide synthase (eNOS) pathway. In summary, simvastatin ameliorates placental hypoperfusion and restores trophoblast function disrupted by aberrant hemodynamics via regulation of endothelial KLF2\/eNOS signaling. These findings highlight simvastatin as a potential therapeutic option for refractory OAPS.<\/jats:p>","DOI":"10.1002\/adhm.202504027","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:23:27Z","timestamp":1772958207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simvastatin Restores Uteroplacental Hemodynamics and Trophoblast Function in Obstetric Antiphospholipid Syndrome in a Placenta\u2010on\u2010a\u2010Chip Model"],"prefix":"10.1002","volume":"15","author":[{"given":"Hongli","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Shandong Provincial Hospital Shandong University  Jinan Shandong China"},{"name":"Department of Obstetrics Weifang Hospital of Traditional Chinese Medicine  Weifang Shandong China"},{"name":"The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine) 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