Document Detail


Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.
MedLine Citation:
PMID:  19075097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; P<0.001), and fetal (2.35+/-0.05 g versus 1.76+/-0.08 g; P<0.001) and placental weight were decreased (0.47+/-0.04 g versus 0.58+/-0.03 g; P<0.01) in the RUPP compared with normal pregnant controls. Serum sEng (0.10+/-0.02 arbitrary pixel units [apu] versus 0.05+/-0.01 apu; P<0.05) and placental endoglin (4.7+/-2.3 apu versus 1.45+/-0.42 apu; P<0.05) were increased along with placental hypoxia inducible factor-1 alpha (1.42+/-0.25 apu versus 0.68+/-0.09 apu; P<0.05) expression in the RUPP versus the normal pregnant dams. Placental HO-1 (1.4+/-0.3 apu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy.
Authors:
Jeffrey S Gilbert; Sara A B Gilbert; Marietta Arany; Joey P Granger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-12-15
Journal Detail:
Title:  Hypertension     Volume:  53     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-23     Completed Date:  2009-02-13     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  399-403     Citation Subset:  IM    
Affiliation:
Department of Physiology, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology
Disease Models, Animal
Female
Heme Oxygenase-1 / metabolism
Hypertension / metabolism*,  physiopathology
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Intracellular Signaling Peptides and Proteins / metabolism*
Ischemia / metabolism*
Placenta / blood supply*
Pre-Eclampsia / etiology,  metabolism
Pregnancy
Pregnancy, Animal / metabolism*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
F32 HL090269-01/HL/NHLBI NIH HHS; HL51971/HL/NHLBI NIH HHS; HL90269/HL/NHLBI NIH HHS; P01 HL051971-165259/HL/NHLBI NIH HHS; R01 HL038499-18/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hif1a protein, rat; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Intracellular Signaling Peptides and Proteins; 0/endoglin protein, rat; EC 1.14.99.3/Heme Oxygenase-1
Comments/Corrections

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