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NIH Research Festival

September 16 – 18, 2015

Endothelial expression of endothelin receptor A in the systemic capillary leak syndrome

Thursday, September 17, 2015 – Poster Session III
3:30 – 5:00 p.m.

FAES Terrace

NIAID

CELLBIO-25

Authors

  • Z Xie
  • AC Sek
  • K Terai
  • LM Long
  • C Nelson
  • AZ Dudek
  • KM Druey

Abstract

Systemic capillary leak syndrome (SCLS) is a rare and potentially fatal vascular disorder characterized by reversible bouts of hypotension and edema. Although spikes in permeability-inducing factors have been linked to acute SCLS flares, whether 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), 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/function of ETA in endothelial cells (ECs) has not been described. To determine the role of ETA in SCLS, we first 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 serum, suggesting a role for ET-1 and ETA in SCLS pathogenesis. However, although ET-1 alone did not induce hyper-permeability of BOEC, an SCLS-related mediator (CXCL10) increased Edrna quantities in BOEC, suggesting a link between SCLS and endothelial ETA. 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 such as sepsis would advance our understanding of vascular integrity mechanisms and potentially uncover new treatment strategies.

Scientific Focus Area: Cell Biology

This page was last updated on Friday, March 26, 2021

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