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Complement Activation and the Resulting Placental Vascular Insufficiency Drives Fetal Growth Restriction Associated with Placental Malaria

Conroy, Andrea L., Silver, Karlee L., Zhong, Kathleen, Rennie, Monique, Ward, Peter, Sarma, J. Vidya, Molyneux, Malcolm E, Sled, John, Fletcher, Joseph F., Rogerson, Stephen and Kain, Kevin C. (2013) 'Complement Activation and the Resulting Placental Vascular Insufficiency Drives Fetal Growth Restriction Associated with Placental Malaria'. Cell Host & Microbe, Vol 13, Issue 2, pp. 215-226.

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Abstract

Placental malaria (PM) is a major cause of fetal growth restriction, yet the underlying mechanism is unclear. Complement C5a and C5a receptor levels are increased with PM. C5a is implicated in fetal growth restriction in non-infection-based animal models. In a case-control study of 492 pregnant Malawian women, we find that elevated C5a levels are associated with an increased risk of delivering a small-for-gestational-age infant. C5a was significantly increased in PM and was negatively correlated with the angiogenic factor angiopoietin-1 and positively correlated with angiopoietin-2, soluble endoglin, and vascular endothelial growth factor. Genetic or pharmacological blockade of C5a or its receptor in a mouse model of PM resulted in greater fetoplacental vessel development, reduced placental vascular resistance, and improved fetal growth and survival. These data suggest that C5a drives fetal growth restriction in PM through dysregulation of angiogenic factors essential for placental vascular remodeling resulting in placental vascular insufficiency.

Item Type: Article
Subjects: QU Biochemistry > Biochemistry of the Human Body > QU 107 Growth substances
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Pregnancy Complications > WQ 240 Pregnancy complications (General)
WS Pediatrics > By Age Groups > WS 420 Newborn infants. Neonatology
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.chom.2013.01.010
Depositing User: Lynn Roberts-Maloney
Date Deposited: 17 Feb 2015 12:02
Last Modified: 06 Feb 2018 13:09
URI: http://archive.lstmed.ac.uk/id/eprint/4913

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