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dc.contributor.authorSek, AC
dc.contributor.authorXie, Z.
dc.contributor.authorTerai, K.
dc.contributor.authorLong, LM
dc.contributor.authorNelson, C.
dc.contributor.authorDudek, AZ
dc.contributor.authorDruey, KM
dc.date.accessioned2015-11-09T16:09:32Z
dc.date.available2015-11-09T16:09:32Z
dc.date.issued2015-07-15
dc.identifier.bibliographicCitationSek, A. C., Xie, Z. H., Terai, K., Long, L. M., Nelson, C., Dudek, A. Z. and Druey, K. M. Endothelial Expression of Endothelin Receptor A in the Systemic Capillary Leak Syndrome. PLoS One. 2015. 10(7). DOI: 10.1371/journal.pone.0133266.en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10027/19873
dc.descriptionThis is the copy of an article published in the PLoS ONE https://creativecommons.org/publicdomain/zero/1.0/en_US
dc.description.abstractIdiopathic systemic capillary leak syndrome (SCLS) is a rare and potentially fatal vascular disorder characterized by reversible bouts of hypotension and edema resulting from fluid and solute escape into soft tissues. Although spikes in permeability-inducing factors have been linked to acute SCLS flares, whether or not they act on an inherently dysfunctional endothelium is unknown. To assess the contribution of endothelial-intrinsic mechanisms in SCLS, we derived blood-outgrowth endothelial cells (BOEC) from patients and healthy controls and examined gene expression patterns. Ednra, encoding Endothelin receptor A (ETA)-the target of Endothelin 1 (ET-1)-was significantly increased in SCLS BOEC compared to healthy controls. Although vasoconstriction mediated by ET-1 through ETA activation on vascular smooth muscle cells has been well characterized, the expression and function of ETA receptors in endothelial cells (ECs) has not been described. To determine the role of ETA and its ligand ET-1 in SCLS, if any, we examined ET-1 levels in SCLS sera and functional effects of endothelial ETA expression. ETA overexpression in EAhy926 endothelioma cells led to ET-1-induced hyper-permeability through canonical mechanisms. Serum ET-1 levels were elevated in acute SCLS sera compared to remission and healthy control sera, suggesting a possible role for ET-1 and ETA in SCLS pathogenesis. However, although ET-1 alone did not induce hyper-permeability of patient-derived BOEC, an SCLS-related mediator (CXCL10) increased Edrna quantities in BOEC, suggesting a link between SCLS and endothelial ETA expression. These results demonstrate that ET-1 triggers classical mechanisms of vascular barrier dysfunction in ECs through ETA. Further studies of the ET-1-ETA axis in SCLS and in more common plasma leakage syndromes including sepsis and filovirus infection would advance our understanding of vascular integrity mechanisms and potentially uncover new treatment strategies.en_US
dc.description.sponsorshipThis study was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI001083 to KMD)en_US
dc.publisherPublic Library of Scienceen_US
dc.titleEndothelial Expression of Endothelin Receptor A in the Systemic Capillary Leak Syndrome.en_US
dc.typeArticleen_US


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