The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction
Open accessAbstract
Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications.
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Citations
Cites
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Circulating angiogenic factors and the risk of preeclampsia
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Circulating angiogenic factors and the risk of preeclampsia*
(2004) · Obstetrics & Gynecology · doi:10.1097/00006250-200405000-00028 · Cited by 2,615
Regulatory T cells mediate maternal tolerance to the fetus
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Cited by
Pre-eclampsia part 1: current understanding of its pathophysiology
Chaiworapongsa, T., Chaemsaithong, P., Yeo, L., & Romero, R. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.102 · Cited by 956
Pathogenesis of antiphospholipid syndrome: understanding the antibodies
Meroni, P. L., Borghi, M. O., Raschi, E., & Tedesco, F. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.52 · Cited by 620
Complement and Its Receptors: New Insights into Human Disease
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Self-citationErez, O., Romero, R., Espinoza, J., Fu, W., Todem, D., Kusanovic, J. P., Gotsch, F., Edwin, S., Nien, J. K., Chaiworapongsa, T., et al. (2008) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050802034545 · Cited by 287
Metadata
- Authors
- Girardi, G., Yarilin, D., Thurman, J. M., Holers, V. M., & Salmon, J. E.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-08-21
- Volume
- 203
- Issue
- 9
- Pages
- 2165-2175
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2140537006
- Cited by
- 508
- References
- 55
- FWCI
- 30.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Girardi, G., Yarilin, D., Thurman, J. M., Holers, V. M., & Salmon, J. E. (2006). Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20061022
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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