Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy
Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1), and placental mitochondrial (mt) dysfunction and oxidative stress (ROS). Progesterone induced blocking factor (PIBF) is a p...
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2021
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oai:doaj.org-article:2dd90e6416b74dd1a0a18ea6cb2c6f3e2021-11-25T17:07:31ZProgesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy10.3390/cells101128172073-4409https://doaj.org/article/2dd90e6416b74dd1a0a18ea6cb2c6f3e2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2817https://doaj.org/toc/2073-4409Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1), and placental mitochondrial (mt) dysfunction and oxidative stress (ROS). Progesterone induced blocking factor (PIBF) is a product of progesterone signaling that blocks inflammatory processes and we have previously shown PIBF to lower mean arterial blood pressure (MAP) and sFlt-1 in a rat model of PE. Infusion of sFlt-1 causes hypertension and many characteristics of PE in pregnant rodents, however, its role in causing mt dysfunction is unknown. Therefore, we hypothesize that PIBF will improve mt function and MAP in response to elevated sFlt-1 during pregnancy. We tested our hypothesis by infusing sFlt-1 via miniosmotic pumps in normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg<sup>−1</sup>·day<sup>−1</sup>) on gestation days (GD) 13–19 in the presence or absence of PIBF (2.0 µg/mL) injected intraperitoneally on GD 15 and examined mean arterial blood pressure (MAP) and placental mt ROS on GD 19. sFlt-1 increased MAP to 112 + 2 (n = 11) compared to NP rats (98 + 2 mmHg, n = 15, <i>p</i> < 0.05), which was lowered in the presence of sFlt-1 (100 + 1 mmHg, n = 5, <i>p</i> < 0.05). Placental mtATP was reduced in sFlt-1 infused rats versus NP controls, but was improved with PIBF. Placental mtROS was elevated with sFlt-1 compared to NP controls, but was reduced with PIBF. Sera from NP + sFlt-1 increased endothelial cell mtROS, which was attenuated with PIBF. These data demonstrate sFlt-1 induced HTN during pregnancy reduces placental mt function. Importantly, PIBF improved placental mt function and HTN, indicating the efficacy of improved progesterone signaling as potential therapeutics for PE.Evangeline DeerJalisa JonesDenise C. CorneliusKyleigh ComleyOwen HerrockNathan CampbellSarah FitzgeraldTarek IbrahimBabbette LaMarcaLorena M. AmaralMDPI AGarticlehypertensionpreeclampsiasFlt-1oxidative stressplacental ischemiaBiology (General)QH301-705.5ENCells, Vol 10, Iss 2817, p 2817 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
hypertension preeclampsia sFlt-1 oxidative stress placental ischemia Biology (General) QH301-705.5 |
| spellingShingle |
hypertension preeclampsia sFlt-1 oxidative stress placental ischemia Biology (General) QH301-705.5 Evangeline Deer Jalisa Jones Denise C. Cornelius Kyleigh Comley Owen Herrock Nathan Campbell Sarah Fitzgerald Tarek Ibrahim Babbette LaMarca Lorena M. Amaral Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| description |
Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1), and placental mitochondrial (mt) dysfunction and oxidative stress (ROS). Progesterone induced blocking factor (PIBF) is a product of progesterone signaling that blocks inflammatory processes and we have previously shown PIBF to lower mean arterial blood pressure (MAP) and sFlt-1 in a rat model of PE. Infusion of sFlt-1 causes hypertension and many characteristics of PE in pregnant rodents, however, its role in causing mt dysfunction is unknown. Therefore, we hypothesize that PIBF will improve mt function and MAP in response to elevated sFlt-1 during pregnancy. We tested our hypothesis by infusing sFlt-1 via miniosmotic pumps in normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg<sup>−1</sup>·day<sup>−1</sup>) on gestation days (GD) 13–19 in the presence or absence of PIBF (2.0 µg/mL) injected intraperitoneally on GD 15 and examined mean arterial blood pressure (MAP) and placental mt ROS on GD 19. sFlt-1 increased MAP to 112 + 2 (n = 11) compared to NP rats (98 + 2 mmHg, n = 15, <i>p</i> < 0.05), which was lowered in the presence of sFlt-1 (100 + 1 mmHg, n = 5, <i>p</i> < 0.05). Placental mtATP was reduced in sFlt-1 infused rats versus NP controls, but was improved with PIBF. Placental mtROS was elevated with sFlt-1 compared to NP controls, but was reduced with PIBF. Sera from NP + sFlt-1 increased endothelial cell mtROS, which was attenuated with PIBF. These data demonstrate sFlt-1 induced HTN during pregnancy reduces placental mt function. Importantly, PIBF improved placental mt function and HTN, indicating the efficacy of improved progesterone signaling as potential therapeutics for PE. |
| format |
article |
| author |
Evangeline Deer Jalisa Jones Denise C. Cornelius Kyleigh Comley Owen Herrock Nathan Campbell Sarah Fitzgerald Tarek Ibrahim Babbette LaMarca Lorena M. Amaral |
| author_facet |
Evangeline Deer Jalisa Jones Denise C. Cornelius Kyleigh Comley Owen Herrock Nathan Campbell Sarah Fitzgerald Tarek Ibrahim Babbette LaMarca Lorena M. Amaral |
| author_sort |
Evangeline Deer |
| title |
Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| title_short |
Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| title_full |
Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| title_fullStr |
Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| title_full_unstemmed |
Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy |
| title_sort |
progesterone induced blocking factor reduces hypertension and placental mitochondrial dysfunction in response to sflt-1 during pregnancy |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/2dd90e6416b74dd1a0a18ea6cb2c6f3e |
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