title: The Endothelin Type A Receptor as a Potential Therapeutic Target in Preeclampsia.
abstract: Preeclampsia (PE) is a disorder of pregnancy typically characterized by new onset hypertension after gestational week 20 and proteinuria. Although PE is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disease remain unclear and treatment options are limited. However, there is increasing evidence to suggest that endothelin-1 (ET-1) plays a critical role in the pathophysiology of PE. Multiple studies report that ET-1 is increased in PE and some studies report a positive correlation between ET-1 and the severity of symptoms. 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 infusion, Tumor necrosis factor (TNF) -α infusion, and Angiotensin II type 1 receptor autoantibody (AT1-AA) infusion) have proven to be susceptible to Endothelin Type A (ETA) receptor antagonism. While the results are promising, further work is needed to determine whether ET antagonists could provide an effective therapy for the management of preeclampsia.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. bbakrania@umc.edu.
authors.forename: Bhavisha
authors.initials: B
authors.lastname: Bakrania
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. jduncan2@umc.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Duncan
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. jpwarrington@umc.edu.
authors.forename: Junie P
authors.initials: JP
authors.lastname: Warrington
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. jgranger@umc.edu.
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D016232:Endothelins / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D065130:Endothelin A Receptor Antagonists; D016232:Endothelins; D044022:Receptor, Endothelin A
keywords: blood pressure; cardiovascular; endothelin; endothelium; hypertension; placenta; preeclampsia; pregnancy; vascular smooth muscle