ArticleMolecular immunology2013
Complement activation is critical for placental ischemia-induced hypertension in the rat.
Article in Molecular immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Complement factor B activation in patients with preeclampsia.Journal of reproductive immunology · 2015Trial
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction.Physiological reports · 2025Article
- The role of complement in normal pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Is the central complement component C3 altered in the synergy of HIV infection and preeclampsia?European journal of obstetrics & gynecology and reproductive biology: X · 2023Article
- The complement system in preeclampsia: a review of its activation and endothelial injury in the triad of COVID-19 infection and HIV-associated preeclampsia.Obstetrics & gynecology science · 2023Article
- The role of immune cells and mediators in preeclampsia.Nature reviews. Nephrology · 2023Review
- Alternative pathway activation in pregnancy, a measured amount "complements" a successful pregnancy, too much results in adverse events.Immunological reviews · 2023Review
- Critical Role for Macrophages in the Developmental Programming of Pancreatic β-Cell Area in Offspring of Hypertensive Pregnancies.Diabetes · 2022Article
- Animal Models of Preeclampsia: Mechanistic Insights and Promising Therapeutics.Endocrinology · 2022Review
- Animal models of preeclampsia: investigating pathophysiology and therapeutic targets.American journal of obstetrics and gynecology · 2022Review
- Placental Ischemia Says "NO" to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia.International journal of molecular sciences · 2021Review
- Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia.American journal of physiology. Heart and circulatory physiology · 2020Review
- Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond.Frontiers in immunology · 2020Review
- Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension.American journal of physiology. Heart and circulatory physiology · 2019Article
- Interactions between the complement and endothelin systems in normal pregnancy and following placental ischemia.Molecular immunology · 2019Article
- Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia.Scientific reports · 2019Article
- The role of the complement system in HIV infection and preeclampsia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Dysregulation of Complement Activation and Placental Dysfunction: A Potential Target to Treat Preeclampsia?Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Preeclampsia is a major obstetric problem defined by new-onset hypertension and proteinuria associated with compromised placental perfusion. Although activation of the complement system is increased in preeclampsia compared to normal pregnancy, it remains unclear whether excess complement activation is a cause or consequence of placental ischemia. Therefore, we hypothesized that complement activation is critical for placental ischemia-induced hypertension. We employed the reduced utero-placental perfusion pressure (RUPP) model of placental ischemia in the rat to induce hypertension in the third trimester and evaluated the effect of inhibiting complement activation with a soluble recombinant form of an endogenous complement regulator, human complement receptor 1 (sCR1; CDX-1135). On day 14 of a 21-day gestation, rats received either RUPP or Sham surgery and 15 mg/kg/day sCR1 or saline intravenously on days 14-18. Circulating complement component 3 decreased and complement activation product C3a increased in RUPP vs. Sham (p<0.05), indicating complement activation had occurred. Mean arterial pressure (MAP) measured on day 19 increased in RUPP vs. Sham rats (109.8±2.8 mmHg vs. 93.6±1.6 mmHg). Treatment with sCR1 significantly reduced elevated MAP in RUPP rats (98.4±3.6 mmHg, p<0.05) and reduced C3a production. Vascular endothelial growth factor (VEGF) decreased in RUPP compared to Sham rats, and the decrease in VEGF was not affected by sCR1 treatment. Thus, these studies have identified a mechanistic link between complement activation and the pregnancy complication of hypertension apart from free plasma VEGF and have identified complement inhibition as a potential treatment strategy for placental ischemia-induced hypertension in preeclampsia.
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Registered trials
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