Cargando…
Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta
BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated recep...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581437/ https://www.ncbi.nlm.nih.gov/pubmed/37702083 http://dx.doi.org/10.1161/HYPERTENSIONAHA.123.21645 |
_version_ | 1785122136231247872 |
---|---|
author | Grimaldi, Brooke Kohan-Ghadr, Hamid-Reza Halari, Chidambra D. Nandi, Pinki Kingdom, John C. Drewlo, Sascha |
author_facet | Grimaldi, Brooke Kohan-Ghadr, Hamid-Reza Halari, Chidambra D. Nandi, Pinki Kingdom, John C. Drewlo, Sascha |
author_sort | Grimaldi, Brooke |
collection | PubMed |
description | BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta. METHODS: We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation. RESULTS: Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 (Hmox1). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner. CONCLUSIONS: Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality. |
format | Online Article Text |
id | pubmed-10581437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-105814372023-10-18 Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta Grimaldi, Brooke Kohan-Ghadr, Hamid-Reza Halari, Chidambra D. Nandi, Pinki Kingdom, John C. Drewlo, Sascha Hypertension Original Articles BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta. METHODS: We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation. RESULTS: Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 (Hmox1). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner. CONCLUSIONS: Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality. Lippincott Williams & Wilkins 2023-09-13 2023-11 /pmc/articles/PMC10581437/ /pubmed/37702083 http://dx.doi.org/10.1161/HYPERTENSIONAHA.123.21645 Text en © 2023 The Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
spellingShingle | Original Articles Grimaldi, Brooke Kohan-Ghadr, Hamid-Reza Halari, Chidambra D. Nandi, Pinki Kingdom, John C. Drewlo, Sascha Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title | Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title_full | Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title_fullStr | Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title_full_unstemmed | Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title_short | Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta |
title_sort | rosiglitazone-mediated activation of pparγ restores ho1 expression in the human preeclamptic placenta |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581437/ https://www.ncbi.nlm.nih.gov/pubmed/37702083 http://dx.doi.org/10.1161/HYPERTENSIONAHA.123.21645 |
work_keys_str_mv | AT grimaldibrooke rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta AT kohanghadrhamidreza rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta AT halarichidambrad rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta AT nandipinki rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta AT kingdomjohnc rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta AT drewlosascha rosiglitazonemediatedactivationofppargrestoresho1expressioninthehumanpreeclampticplacenta |