Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia
IntroductionPreeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Stud...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Reproductive Health |
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| author | Neelima Chandra Thomas D. Kimble Kathleen R. Heim Sharon M. Anderson Andrew P. Wong Andrea R. Thurman Gustavo F. Doncel |
| author_facet | Neelima Chandra Thomas D. Kimble Kathleen R. Heim Sharon M. Anderson Andrew P. Wong Andrea R. Thurman Gustavo F. Doncel |
| author_sort | Neelima Chandra |
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| description | IntroductionPreeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.MethodsIn this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.ResultsAmong the inflammatory mediators, we found a significant elevation in the expression of receptors of advanced glycation end products (RAGE) and two of its damage-associated molecular pattern proteins (DAMPs) and ligands, the high mobility group box protein HMGB1 and the calcium binding protein S100, in preeclamptic tissues as compared to normal placentas. In addition, we observed a significant increase in the master pro-inflammatory transcription factor, nuclear factor kappa B p65 subunit (NFκB), as well as non-significant increases in cyclooxygenase 2 (COX-2) and interleukin 8 (IL-8) in the PE group.ConclusionThis study provides insight into the relationship of tissue inflammatory mediators with severe preeclampsia and the RAGE associated signaling complex, suggesting a pathogenic role for this pathway which has clinical implications for the understanding, diagnosis, and potential novel therapeutic approaches to the syndrome. |
| format | Article |
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| institution | Kabale University |
| issn | 2673-3153 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Reproductive Health |
| spelling | doaj-art-a0b00a2fd22a49edaf35c4bb3fe96cff2025-08-20T03:40:33ZengFrontiers Media S.A.Frontiers in Reproductive Health2673-31532025-08-01710.3389/frph.2025.15876991587699Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsiaNeelima Chandra0Thomas D. Kimble1Kathleen R. Heim2Sharon M. Anderson3Andrew P. Wong4Andrea R. Thurman5Gustavo F. Doncel6CONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United StatesDepartment of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, United StatesVHC Health Physicians, Charlotte S. Benjamin Center for Women’s Health, Arlington, VA, United StatesCONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United StatesCONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United StatesCONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United StatesCONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United StatesIntroductionPreeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.MethodsIn this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.ResultsAmong the inflammatory mediators, we found a significant elevation in the expression of receptors of advanced glycation end products (RAGE) and two of its damage-associated molecular pattern proteins (DAMPs) and ligands, the high mobility group box protein HMGB1 and the calcium binding protein S100, in preeclamptic tissues as compared to normal placentas. In addition, we observed a significant increase in the master pro-inflammatory transcription factor, nuclear factor kappa B p65 subunit (NFκB), as well as non-significant increases in cyclooxygenase 2 (COX-2) and interleukin 8 (IL-8) in the PE group.ConclusionThis study provides insight into the relationship of tissue inflammatory mediators with severe preeclampsia and the RAGE associated signaling complex, suggesting a pathogenic role for this pathway which has clinical implications for the understanding, diagnosis, and potential novel therapeutic approaches to the syndrome.https://www.frontiersin.org/articles/10.3389/frph.2025.1587699/fullcalcium binding protein (S-100)cyclooxygenase 2 (COX-2)high mobility group box protein (HMGB1)interleukin 8 (IL-8)nuclear factor kappa B p65 sub unit (NF-kBp65)receptors of advanced glycation end products (RAGE) |
| spellingShingle | Neelima Chandra Thomas D. Kimble Kathleen R. Heim Sharon M. Anderson Andrew P. Wong Andrea R. Thurman Gustavo F. Doncel Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia Frontiers in Reproductive Health calcium binding protein (S-100) cyclooxygenase 2 (COX-2) high mobility group box protein (HMGB1) interleukin 8 (IL-8) nuclear factor kappa B p65 sub unit (NF-kBp65) receptors of advanced glycation end products (RAGE) |
| title | Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| title_full | Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| title_fullStr | Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| title_full_unstemmed | Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| title_short | Inflammatory mediators and the RAGE pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| title_sort | inflammatory mediators and the rage pathway in placental tissues of pregnancies complicated by severe preeclampsia |
| topic | calcium binding protein (S-100) cyclooxygenase 2 (COX-2) high mobility group box protein (HMGB1) interleukin 8 (IL-8) nuclear factor kappa B p65 sub unit (NF-kBp65) receptors of advanced glycation end products (RAGE) |
| url | https://www.frontiersin.org/articles/10.3389/frph.2025.1587699/full |
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