2016-03-01
Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment
Publication
Publication
Current Opinion in Nephrology & Hypertension , Volume 25 - Issue 2 p. 94- 99
Purpose of review
Preeclampsia is a systemic, pregnancy-related disorder featuring hypertension and proteinuria arising from
placental overproduction of soluble FMS-like tyrosine kinase-1, resulting in an antiangiogenic state because
of the inhibition of the vascular endothelial growth factor (VEGF) family. Similarly, antiangiogenetic
treatment aimed at targeting VEGF in patients with cancer is associated with a preeclampsia-like syndrome.
In this study we discuss the pathophysiological role of an activated endothelin system in both conditions.
Recent findings
In different experimental forms of preeclampsia, in clinical preeclampsia, and in cancer patients on
antiangiogenic treatment, activation of the endothelin axis invariably occurs and this activation is directly
related to the circulating level of sFlt-1 or the intensity of antiangiogenic treatment. Administration of
endothelin receptor A-selective or dual endothelin receptor antagonists can prevent or largely attenuate the
hypertension and proteinuria in experimental forms of preeclampsia, as well as in rats exposed to receptor
tyrosine-kinase inhibitors targeting VEGF-signaling, supporting the concept that activation of the endothelin
axis plays a key role in the manifestations of these disorders.
Summary
Activation of the endothelin axis has now emerged as a crucial player in the manifestations of
preeclampsia and following antiangiogenic treatment. As a consequence, blockade of the endothelin
system may be considered as a treatment option both in preeclampsia and in antiangiogenesis-induced
hypertension and renal toxicity in patients with cancer.
Additional Metadata | |
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doi.org/10.1097/MNH.0000000000000197, hdl.handle.net/1765/85970 | |
Current Opinion in Nephrology & Hypertension | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
Saleh, L., Danser, J., & van den Meiracker, A. (2016). Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment. Current Opinion in Nephrology & Hypertension (Vol. 25, pp. 94–99). doi:10.1097/MNH.0000000000000197 |