biostudies-literatureChow RPUtenriksdepartementetEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSQueen&apos;s University BelfastDepartment for International Development, UK GovernmentUSAIDNational Institutes of HealthBill and Melinda Gates FoundationNational Institute of Child Health and Human Development177138https://www.ebi.ac.uk/biostudies/studies/S-EPMC11634635biostudies-literatureUnknown986<h4>Background</h4>Preeclampsia is prevalent in women with diabetes, but the mechanism is unclear. We previously found that oxidized, glycated lipoproteins robustly upregulated soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. Here, we determined the role of protein kinase C (PKC) and its subtypes in sFlt1 regulation in placental trophoblasts, and whether this mechanism might mediate the effect of modified lipoproteins.<h4>Methods</h4>Cultured human HTR8/SVneo and BeWo trophoblasts were treated with the PKC activator phorbol-12-myristate-13-acetate (PMA) for 24h, ± PKC inhibitors GF109203X (general), Ro31-8220 (PKCα-selective), LY333531 (PKCβ-selective) and rottlerin (PKCδ-selective). The effect of 'heavily oxidized, glycated' low-density lipoproteins (HOG-LDL) vsEuropean journal of pharmacologyModified lipoprotein-induced sFlt1 production in human placental trophoblasts is mediated by protein kinase C.PMC11634635R01 HD0965010703-03Li YLyons TJYu JYCurtis TMChow RPZhao JfalseModified lipoprotein-induced sFlt1 production in human placental trophoblasts is mediated by protein kinase C.<h4>Background</h4>Preeclampsia is prevalent in women with diabetes, but the mechanism is unclear. We previously found that oxidized, glycated lipoproteins robustly upregulated soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. Here, we determined the role of protein kinase C (PKC) and its subtypes in sFlt1 regulation in placental trophoblasts, and whether this mechanism might mediate the effect of modified lipoproteins.<h4>Methods</h4>Cultured human HTR8/SVneo and BeWo trophoblasts were treated with the PKC activator phorbol-12-myristate-13-acetate (PMA) for 24h, ± PKC inhibitors GF109203X (general), Ro31-8220 (PKCα-selective), LY333531 (PKCβ-selective) and rottlerin (PKCδ-selective). The effect of 'heavily oxidized, glycated' low-density lipoproteins (HOG-LDL) vs2025-01-01T00:00:00Z2025 Jan2026-06-06T10:23:35.315Z2026-05-28T03:13:22.138ZS-EPMC116346353955133810.1016/j.ejphar.2024.177138