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In preeclampsia endogenous cardiotonic steroids induce vascular fibrosis and impair relaxation of umbilical arteries.

AbstractBACKGROUND:
Marinobufagenin (MBG), a bufadienolide cardiotonic steroid, induces cardiovascular fibrosis. Because levels of MBG in preeclampsia are increased, and anti-MBG monoclonal antibody reduces blood pressure (BP) in a rat model of preeclampsia, we hypothesized that in preeclampsia, elevated MBG levels would be associated with the development of fibrosis in feto-placental circulation and with impairment of vascular relaxation.
METHOD:
We studied 16 patients with preeclampsia (systolic BP=150±4 mmHg; 28±2 years, 37±1 weeks gestational age) and 14 gestational age-matched normal pregnant women (systolic BP=112±2 mmHg).
RESULTS:
Preeclampsia was associated with a rise in plasma and placental levels of MBG. In preeclamptic umbilical arteries, the expression of Fli-1, a transcription factor and a negative regulator of fibrosis, was significantly reduced (P<0.001), whereas procollagen-1 expression was increased (P<0.01). As compared to control vessels, isolated rings of umbilical arteries from patients with preeclampsia demonstrated unaltered responsiveness to endothelin-1 (EC50=2.2 and 3.2 nmol/l, respectively), but exhibited an impaired response to the relaxant effect of sodium nitroprusside (EC50=1.5 vs. 32.4 nmol/l, P<.001) following endothelin-1-induced constriction. Ex-vivo treatment of normal umbilical arteries explants with 1 and 10 nmol/l MBG for 24 h mimicked the effects of preeclampsia, specifically suppressed Fli-1 and increased collagen-1 expression while impairing vasorelaxation.
CONCLUSION:
Our results indicate that in preeclampsia, elevated levels of MBG induce vascular fibrosis via a Fli-1-dependent mechanism which leads to an impairment of vasorelaxation, and suggest that MBG represents a potential target for therapy of this syndrome.
AuthorsElena R Nikitina, Anton V Mikhailov, Ekaterina S Nikandrova, Elena V Frolova, Artem V Fadeev, Vera V Shman, Victoria Y Shilova, Natalia I Tapilskaya, Joseph I Shapiro, Olga V Fedorova, Alexei Y Bagrov
JournalJournal of hypertension (J Hypertens) Vol. 29 Issue 4 Pg. 769-76 (Apr 2011) ISSN: 1473-5598 [Electronic] England
PMID21330936 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Steroids
Topics
  • Adult
  • Blotting, Western
  • Female
  • Humans
  • Immunoassay
  • Pre-Eclampsia (metabolism)
  • Pregnancy
  • Steroids (metabolism)
  • Umbilical Arteries (metabolism, pathology, physiopathology)

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