title: Endothelin as a final common pathway in the pathophysiology of preeclampsia:  therapeutic implications.
abstract: OBJECTIVE
  Preeclampsia remains a major health concern in the United States and worldwide. Recent research has begun to shed light on the underlying mechanisms responsible for the symptoms of preeclampsia, and may provide new avenues for therapy for the preeclamptic patient.
  
  
  RESULTS
  The central role of placental ischemia in the manifestation of preeclampsia has provided new understanding for the origin of pathogenic factors in the preeclamptic patient. The release of soluble factors into the maternal bloodstream from the ischemic placenta is now recognized as a central mechanism in disease manifestation. Specifically, the importance of the vascular endothelial growth factor antagonist soluble fms-like tyrosine kinase and immune factors as factors regulating maternal endothelial dysfunction has become widely acknowledged. Furthermore, mounting evidence implicates the signaling protein endothelin-1 as the final converging factor in the multifaceted cascades that are responsible for the symptomatic manifestation of preeclampsia. Endothelin-1, as a final common pathway in the pathogenic cascade of preeclampsia, presents an intriguing new therapeutic approach for preeclamptic patients.
  
  
  CONCLUSIONS
  Identification of antiangiogenic, autoimmune, and inflammatory factors produced in response to placental ischemia have provided potential new avenues for future research into novel therapies for the preeclamptic patient, and suggest new therapeutic avenues for the treatment of preeclampsia.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. jgranger@umc.edu
authors.forename: Eric M
authors.initials: EM
authors.lastname: George
authors.forename: Ana C
authors.initials: AC
authors.lastname: Palei
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D056704:Adaptive Immunity; D020533:Angiogenesis Inhibitors; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007511:Ischemia / Q000150:complications*; D010920:Placenta / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D019332:Endothelin-1; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1