55 research outputs found
The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia
Growth-restricted fetuses are at risk for a variety of lifelong medical conditions. Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is associated with fetuses who suffer from intrauterine growth restriction (IUGR). Recently, emerging evidence indicates that preeclamptic women harbor AT1 receptor agonistic autoantibodies (AT1-AAs) that contribute to the disease features. However, the exact role of AT1-AAs in IUGR and the underlying mechanisms have not been identified. We report that these autoantibodies are present in the cord blood of women with preeclampsia and retain the ability to activate AT1 receptors. Using an autoantibody-induced animal model of preeclampsia, we show that AT1-AAs cross the mouse placenta, enter fetal circulation, and lead to small fetuses with organ growth retardation. AT1-AAs also induce apoptosis in the placentas of pregnant mice, human villous explants, and human trophoblast cells. Finally, autoantibody-induced IUGR and placental apoptosis are diminished by either losartan or an autoantibody-neutralizing peptide. Thus, these studies identify AT1-AA as a novel causative factor of preeclampsia-associated IUGR and offer two possible underlying mechanisms: a direct detrimental effect on fetal development by crossing the placenta and entering fetal circulation, and indirectly through AT1-AA–induced placental damage. Our findings highlight AT1-AAs as important therapeutic targets
Modulation of gut microbiota downregulates the development of food allergy in infancy
In humans, microbial colonisation of the intestine begins just after
birth. However, development of the normal flora is a gradual process,
which is initially determined by factors such as genetic aspects, the
maternal-foetal interaction, place and mode of delivery, early feedings
strategies, and the use of antibiotics. Current knowledge on the
significance and impact of the gut microflora on the development of the
gut immune system indicates that a close relationship between allergic
sensitisation and the development of the intestinal microflora may occur
in infancy. Intestinal micro-organisms could downregulate the allergic
inflammation by counterbalancing type 2 T-helper cell responses and by
enhancing allergen exclusion through an immunological response. (C) 2013
SEICAP. Published by Elsevier Espana, S.L. All rights reserved
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