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Role of complement component C1q in the onset of preeclampsia in mice.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2011 Oct; Vol. 58 (4), pp. 716-24. Date of Electronic Publication: 2011 Aug 22. - Publication Year :
- 2011
-
Abstract
- Preeclampsia (PE) is a life-threatening, pregnancy-induced disease and a leading cause of maternal and fetal morbidity and mortality. Despite considerable research, the causes of PE remain unclear, and there is no effective treatment. Studies in animal models that resemble this complex pregnancy-related disorder may help to identify possible therapies for PE. Complement component C1q has an important role in trophoblast migration, spiral arteries remodeling, and normal placentation. Here we show that pregnant C1q-deficient (C1q(-/-)) mice recapitulate the key features of human PE: hypertension, albuminuria, endotheliosis, decreased placental vascular endothelial growth factor (VEGF) and elevated levels of soluble VEGF receptor 1 (sFlt-1) that correlate with increased fetal death. In addition, decreased blood flow and increased oxidative stress are observed in placentas from C1q(-/-) mice. Treatment of C1q(-/-) mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of PE. Serum-soluble receptors for VEGF-1 levels were reduced and placental VEGF levels were significantly increased in C1q(-/-) mice treated with pravastatin compared with untreated C1q(-/-) mice (VEGF: 1067±171 versus 419±194 pg/mL; P<0.01). Pravastatin treatment reduced hypertension (change in mean arterial pressure: 1±1 versus 18±3 mm Hg in C1q(-/-) untreated mice), and albuminuria (of creatinine) was reduced from 820±175 to 117±45 μg/mg (both P<0.01). Renal damage and endothelial dysfunction were significantly attenuated with pravastatin. This model that highlights the causative role of impaired trophoblast invasion in the pathogenesis of PE allowed us to identify pravastatin as a good therapeutic option to prevent PE.
- Subjects :
- Animals
Blood Pressure physiology
Cell Movement drug effects
Collagenases metabolism
Complement C1q deficiency
Complement C1q genetics
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Mice
Mice, Knockout
Placenta blood supply
Placenta metabolism
Pravastatin pharmacology
Pravastatin therapeutic use
Pre-Eclampsia metabolism
Pre-Eclampsia prevention & control
Pregnancy
Regional Blood Flow drug effects
Regional Blood Flow physiology
Trophoblasts cytology
Vascular Endothelial Growth Factor A metabolism
Vascular Endothelial Growth Factor Receptor-1 metabolism
Complement C1q physiology
Disease Models, Animal
Pre-Eclampsia physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 58
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 21859968
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.111.175919