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Increased Tissue Endothelin-1 and Endothelin-B Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis.

Dimitrijevic, Ivan LU ; Andersson, Christina; Rissler, Pehr LU and Edvinsson, Lars LU (2010) In Ophthalmology 117. p.628-636
Abstract
PURPOSE: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA. DESIGN: Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: The study included 10 patients with GCA and 10 control... (More)
PURPOSE: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA. DESIGN: Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: The study included 10 patients with GCA and 10 control patients with clinically suspected GCA but diagnosed not to have GCA. METHODS: Immunohistochemistry, with anti ET-1, anti-ET(A), and anti-ET(B) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: Endothelin-1, ET(A), and ET(B) receptor immunostaining intensities were quantified. RESULTS: Temporal arteries from the patients with GCA showed the typical histologic features, including intimal thickening, disruption or loss of the elastic lamina, and inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant cells. These features were associated with increased ET-1 and ET(B) receptor immunoreactivity in the medial layer of the temporal arteries and endothelial cells in patients with GCA compared with the controls. The increased ET-1 and ET(B) receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs) and multinucleated giant cells. The ET-1 and ET(B) receptor immunoreactivity correlated with the degree of systemic inflammation. No changes were observed in ET(A) receptor expression in SMCs or endothelial cells compared with controls. CONCLUSIONS: The results suggest a role for ET-1 and ET(B) receptors in GCA. Inhibiting the ET system may provide a corticosteroid-sparing alternative in the treatment of GCA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Ophthalmology
volume
117
pages
628 - 636
publisher
Elsevier
external identifiers
  • wos:000275101000032
  • pmid:20036012
  • scopus:77049111525
ISSN
1549-4713
DOI
10.1016/j.ophtha.2009.07.043
language
English
LU publication?
yes
id
78d2eecc-2b4f-4918-94f3-7d585bbc7aa6 (old id 1523277)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20036012?dopt=Abstract
date added to LUP
2010-01-11 13:48:00
date last changed
2018-05-29 10:14:46
@article{78d2eecc-2b4f-4918-94f3-7d585bbc7aa6,
  abstract     = {PURPOSE: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA. DESIGN: Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: The study included 10 patients with GCA and 10 control patients with clinically suspected GCA but diagnosed not to have GCA. METHODS: Immunohistochemistry, with anti ET-1, anti-ET(A), and anti-ET(B) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: Endothelin-1, ET(A), and ET(B) receptor immunostaining intensities were quantified. RESULTS: Temporal arteries from the patients with GCA showed the typical histologic features, including intimal thickening, disruption or loss of the elastic lamina, and inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant cells. These features were associated with increased ET-1 and ET(B) receptor immunoreactivity in the medial layer of the temporal arteries and endothelial cells in patients with GCA compared with the controls. The increased ET-1 and ET(B) receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs) and multinucleated giant cells. The ET-1 and ET(B) receptor immunoreactivity correlated with the degree of systemic inflammation. No changes were observed in ET(A) receptor expression in SMCs or endothelial cells compared with controls. CONCLUSIONS: The results suggest a role for ET-1 and ET(B) receptors in GCA. Inhibiting the ET system may provide a corticosteroid-sparing alternative in the treatment of GCA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
  author       = {Dimitrijevic, Ivan and Andersson, Christina and Rissler, Pehr and Edvinsson, Lars},
  issn         = {1549-4713},
  language     = {eng},
  pages        = {628--636},
  publisher    = {Elsevier},
  series       = {Ophthalmology},
  title        = {Increased Tissue Endothelin-1 and Endothelin-B Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis.},
  url          = {http://dx.doi.org/10.1016/j.ophtha.2009.07.043},
  volume       = {117},
  year         = {2010},
}