TY - JOUR
T1 - Malaria in pregnancy alters l-arginine bioavailability and placental vascular development
AU - Mcdonald, Chloe R.
AU - Cahill, Lindsay S.
AU - Gamble, Joel R.
AU - Elphinstone, Robyn
AU - Gazdzinski, Lisa M.
AU - Zhong, Kathleen J.Y.
AU - Philson, Adrienne C.
AU - Madanitsa, Mwayiwawo
AU - Kalilani-Phiri, Linda
AU - Mwapasa, Victor
AU - Ter Kuile, Feiko
AU - Sled, John G.
AU - Conroy, Andrea L.
AU - Kain, Kevin C.
PY - 2018/3/7
Y1 - 2018/3/7
N2 - Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis. We hypothesized that hypoarginemia contributes to the pathophysiology of MIP and that l-arginine supplementation would improve birth outcomes. In a prospective study of pregnant Malawian women, we show that MIP was associated with lower concentrations of l-arginine and higher concentrations of endogenous inhibitors of NO biosynthesis, asymmetric and symmetric dimethylarginine, which were associated with adverse birth outcomes. In a model of experimental MIP, l-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls. The mechanism of action was via normalized angiogenic pathways and enhanced placental vasc
AB - Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis. We hypothesized that hypoarginemia contributes to the pathophysiology of MIP and that l-arginine supplementation would improve birth outcomes. In a prospective study of pregnant Malawian women, we show that MIP was associated with lower concentrations of l-arginine and higher concentrations of endogenous inhibitors of NO biosynthesis, asymmetric and symmetric dimethylarginine, which were associated with adverse birth outcomes. In a model of experimental MIP, l-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls. The mechanism of action was via normalized angiogenic pathways and enhanced placental vasc
U2 - 10.1126/scitranslmed.aan6007
DO - 10.1126/scitranslmed.aan6007
M3 - Article
SN - 1946-6234
VL - 10
SP - eaan6007
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 431
M1 - eaan6007
ER -
