Journal article
Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria
AL Conroy, KL Silver, K Zhong, M Rennie, P Ward, JV Sarma, ME Molyneux, J Sled, JF Fletcher, S Rogerson, KC Kain
Cell Host and Microbe | CELL PRESS | Published : 2013
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 re..
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Awarded by Genome Canada
Funding Acknowledgements
We thank all the women for participating in this study as well as the study team for their effort. This work was supported by Global Alliance to Prevent Preterm Birth and Still birth and Grand Challenges in Global Health: Preventing Preterm Birth Initiative grant number 12003 (K. C. K.); the Canadian Institutes of Health Research (CIHR) MOP-115160 and 13721 (K. C. K.), Canada Research Chair (K. C. K.), and Doctoral Research Award (A. L. C.); Genome Canada through the Ontario Genomics Institute (K. C. K.); and a MITACS Elevate Postdoctoral Fellowship (K. L. S.). S.J.R. was supported by a Wellcome Trust Senior Research Fellowship. The funding source had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.