4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA
Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclo...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Artery Research |
| Online Access: | https://www.atlantis-press.com/article/125930006/view |
| _version_ | 1818572295306739712 |
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| author | Olga Fedorova Natalia Aglakova Yulia Grigorova Vitalily Reznik Valintina Zernetkina Wen Wei Edward Lakatta Alexei Bagrov |
| author_facet | Olga Fedorova Natalia Aglakova Yulia Grigorova Vitalily Reznik Valintina Zernetkina Wen Wei Edward Lakatta Alexei Bagrov |
| author_sort | Olga Fedorova |
| collection | DOAJ |
| description | Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.
Objectives and Methods: We hypothesized that in PE, elevated placental MBG levels is associated with development of fibrosis of umbilical arteries. Thirty patients with PE (mean BP = 118 ± 4 mmHg; 29 ± 2 years; 35 weeks gest. age) and 26 gestational age-matched normal pregnant subjects (mean BP = 92 ± 2 mmHg; controls) were enrolled in the clinical study.
Results: PE was associated with a higher placental MBG level (48.6 ± 7.0 vs. 13.6 ± 2.5 nmol/g; P < .01), four-fold decrease of Fli1 and two-fold increase of collagen-1 in placentae (P < .01) vs. control. PE was associated with five-fold decrease in Fli1 level and two-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (P < .01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired response to the relaxant effect of sodium nitroprusside, vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0.9 nmol/L; P < .001). In vitro 10 nmol MBG mimicked effect of PE, and monoclonal anti-MBG antibody reversed this effect.
Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis umbilical arteries in PE. |
| first_indexed | 2024-12-14T18:55:15Z |
| format | Article |
| id | doaj.art-0c53e16422f44d8da51c1fa67b8eb728 |
| institution | Directory Open Access Journal |
| issn | 1876-4401 |
| language | English |
| last_indexed | 2024-12-14T18:55:15Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Artery Research |
| spelling | doaj.art-0c53e16422f44d8da51c1fa67b8eb7282022-12-21T22:51:06ZengBMCArtery Research1876-44012018-12-012410.1016/j.artres.2018.10.0474.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIAOlga FedorovaNatalia AglakovaYulia GrigorovaVitalily ReznikValintina ZernetkinaWen WeiEdward LakattaAlexei BagrovBackground: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. Objectives and Methods: We hypothesized that in PE, elevated placental MBG levels is associated with development of fibrosis of umbilical arteries. Thirty patients with PE (mean BP = 118 ± 4 mmHg; 29 ± 2 years; 35 weeks gest. age) and 26 gestational age-matched normal pregnant subjects (mean BP = 92 ± 2 mmHg; controls) were enrolled in the clinical study. Results: PE was associated with a higher placental MBG level (48.6 ± 7.0 vs. 13.6 ± 2.5 nmol/g; P < .01), four-fold decrease of Fli1 and two-fold increase of collagen-1 in placentae (P < .01) vs. control. PE was associated with five-fold decrease in Fli1 level and two-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (P < .01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired response to the relaxant effect of sodium nitroprusside, vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0.9 nmol/L; P < .001). In vitro 10 nmol MBG mimicked effect of PE, and monoclonal anti-MBG antibody reversed this effect. Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis umbilical arteries in PE.https://www.atlantis-press.com/article/125930006/view |
| spellingShingle | Olga Fedorova Natalia Aglakova Yulia Grigorova Vitalily Reznik Valintina Zernetkina Wen Wei Edward Lakatta Alexei Bagrov 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA Artery Research |
| title | 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA |
| title_full | 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA |
| title_fullStr | 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA |
| title_full_unstemmed | 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA |
| title_short | 4.8 PLACENTAL NA/K-ATPASE INHIBITOR MARINOBUFAGENIN INDUCES ARTERIAL WALL FIBROSIS IN PREECLAMPSIA |
| title_sort | 4 8 placental na k atpase inhibitor marinobufagenin induces arterial wall fibrosis in preeclampsia |
| url | https://www.atlantis-press.com/article/125930006/view |
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