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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria
Cell Host and Microbe, Volume 13, No. 2, Year 2013
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Description
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. © 2013 Elsevier Inc.
Authors & Co-Authors
Conroy, Andrea L.
Canada, Toronto
Toronto General Hospital
Canada, Toronto
University of Toronto
Silver, Karlee L.
Canada, Toronto
Toronto General Hospital
Zhong, Kathleen J.Y.
Canada, Toronto
Toronto General Hospital
Rennie, Monique
Canada, Toronto
Hospital for Sick Children University of Toronto
Canada, Toronto
University of Toronto
Ward, Peter
United States, Ann Arbor
University of Michigan, Ann Arbor
Sarma, J. Vidya
United States, Ann Arbor
University of Michigan, Ann Arbor
Molyneux, Malcolm Edward
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
Malawi, Zomba
University of Malawi
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Sled, John G.
Canada, Toronto
Hospital for Sick Children University of Toronto
Canada, Toronto
University of Toronto
Fletcher, Joseph F.
Canada, Toronto
University of Toronto
Rogerson, Stephen J.
Australia, Melbourne
University of Melbourne
Kain, Kevin C.
Canada, Toronto
Toronto General Hospital
Canada, Toronto
University of Toronto
Statistics
Citations: 118
Authors: 11
Affiliations: 8
Identifiers
Doi:
10.1016/j.chom.2013.01.010
ISSN:
19313128
e-ISSN:
19346069
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Case-Control Study
Participants Gender
Female