Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia
Open Access
- 1 January 2017
- journal article
- review article
- Published by Bioscientifica in Journal of Endocrinology
- Vol. 232 (1), R27-R44
- https://doi.org/10.1530/joe-16-0340
Abstract
Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.Keywords
This publication has 129 references indexed in Scilit:
- An unexpected tail of VEGF and PlGF in pre-eclampsiaBiochemical Society Transactions, 2011
- STAT1 as a novel therapeutical target in pro-atherogenic signal integration of IFNγ, TLR4 and IL-6 in vascular diseaseCytokine & Growth Factor Reviews, 2011
- Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and ChildrenEuropean Heart Journal, 2011
- Pregnancy Enhances Sustained Ca2+ Bursts and Endothelial Nitric Oxide Synthase Activation in Ovine Uterine Artery Endothelial Cells Through Increased Connexin 43 Function1Biology of Reproduction, 2010
- REVIEW ARTICLE: Inflammation and ImplantationAmerican Journal of Reproductive Immunology, 2009
- De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesisProceedings of the National Academy of Sciences of the United States of America, 2009
- Effects of Combined Phosphorylation at Ser-617 and Ser-1179 in Endothelial Nitric-oxide Synthase on EC50(Ca2+) Values for Calmodulin Binding and Enzyme ActivationOnline Journal of Public Health Informatics, 2009
- Regulatory Role of G Protein–Coupled Estrogen Receptor for Vascular Function and ObesityCirculation Research, 2009
- Maternal Uterine Vascular Remodeling During PregnancyPhysiology, 2009
- Uterine DCs are crucial for decidua formation during embryo implantation in miceJCI Insight, 2008