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The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia

  • Preeclampsia (VD Garovic, Section Editor)
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Abstract

Purpose of Review

Preeclampsia (PE) is a disorder of pregnancy typically characterized by new-onset hypertension and proteinuria after gestational week 20. Although preeclampsia is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disorder remain unclear and treatment options are limited. Placental ischemic events and the release of placental factors appear to play a critical role in the pathophysiology. These factors contribute to a generalized systemic vascular endothelial dysfunction and result in increased systemic vascular resistance and hypertension.

Recent Findings

There is increasing evidence to suggest that endothelin-1 (ET-1) in the maternal vascular endothelium is a critical final common pathway, whereby placental ischemic factors cause cardiovascular and renal dysfunction in the mother. Multiple studies report increased levels of ET-1 in PE. A number of experimental models of PE are also associated with elevated tissue levels of prepro-ET-1 mRNA. Moreover, experimental models of PE (placental ischemia, sFlt-1 excess, TNF-α excess, and AT1-AA infusion) have proven to be responsive to ET type A receptor antagonism. Recent studies also suggest that abnormalities in ET type B receptor signaling may also play a role in PE.

Summary

Although numerous studies highlight the importance of the ET system in the pathogenesis of PE, further work is needed to determine whether ET receptor antagonists could provide an effective therapy for the management of this disease.

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Acknowledgments

This work was supported by funds in a grant awarded to JPG from the NHLBI (5P01HL051971, 5R01HL108618, 5T32HL105324) and to FTS from NHLBI (4R00HL130577-02).

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Authors and Affiliations

  1. Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Joey P. Granger, Frank T. Spradley & Bhavisha A. Bakrania

  2. Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Joey P. Granger, Frank T. Spradley & Bhavisha A. Bakrania

  3. Department of Surgery, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Frank T. Spradley

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Granger, J.P., Spradley, F.T. & Bakrania, B.A. The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia. Curr Hypertens Rep 20, 32 (2018). https://doi.org/10.1007/s11906-018-0828-4

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