Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment
Abstract Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease pr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01993-w |
| _version_ | 1818431044997611520 |
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| author | Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Minh Deo Sally Beard Tuong V. Nguyen Kirsten R. Palmer Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_facet | Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Minh Deo Sally Beard Tuong V. Nguyen Kirsten R. Palmer Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_sort | Natalie J. Hannan |
| collection | DOAJ |
| description | Abstract Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1β in trophoblasts. IL-6, IL-1β and TNFα secretion were also significantly reduced. In HUVECs, resveratrol significantly increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not significantly alter HO-1 protein expression, whilst reducing HO-1 protein in trophoblast. Endothelial dysfunction was induced in HUVECs using TNFα, increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral blood mononuclear cells, both of which were increased further by resveratrol. In contrast, resveratrol significantly reduced TNFα-induced Endothelin-1 (a vasoconstrictor) and significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti-angiogenic factors however its effects on the endothelium are mixed. Overall, it may have potential as a treatment for preeclampsia. |
| first_indexed | 2024-12-14T15:43:03Z |
| format | Article |
| id | doaj.art-06e347e9d96a43948751473159437769 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:43:03Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-06e347e9d96a439487514731594377692022-12-21T22:55:34ZengNature PortfolioScientific Reports2045-23222017-05-017111310.1038/s41598-017-01993-wResveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatmentNatalie J. Hannan0Fiona C. Brownfoot1Ping Cannon2Minh Deo3Sally Beard4Tuong V. Nguyen5Kirsten R. Palmer6Stephen Tong7Tu’uhevaha J. Kaitu’u-Lino8Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneDepartment of Obstetrics and Gynaecology, Monash University, Monash Medical CentreTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneTranslational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of MelbourneAbstract Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1β in trophoblasts. IL-6, IL-1β and TNFα secretion were also significantly reduced. In HUVECs, resveratrol significantly increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not significantly alter HO-1 protein expression, whilst reducing HO-1 protein in trophoblast. Endothelial dysfunction was induced in HUVECs using TNFα, increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral blood mononuclear cells, both of which were increased further by resveratrol. In contrast, resveratrol significantly reduced TNFα-induced Endothelin-1 (a vasoconstrictor) and significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti-angiogenic factors however its effects on the endothelium are mixed. Overall, it may have potential as a treatment for preeclampsia.https://doi.org/10.1038/s41598-017-01993-w |
| spellingShingle | Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Minh Deo Sally Beard Tuong V. Nguyen Kirsten R. Palmer Stephen Tong Tu’uhevaha J. Kaitu’u-Lino Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment Scientific Reports |
| title | Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment |
| title_full | Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment |
| title_fullStr | Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment |
| title_full_unstemmed | Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment |
| title_short | Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment |
| title_sort | resveratrol inhibits release of soluble fms like tyrosine kinase sflt 1 and soluble endoglin and improves vascular dysfunction implications as a preeclampsia treatment |
| url | https://doi.org/10.1038/s41598-017-01993-w |
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