Increased tissue endothelin-1 and endothelin-B receptor expression in temporal arteries from patients with giant cell arteritis.
OBJECTIVE
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.


METHODS
Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue.


METHODS
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.


METHODS
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.
Dimitrijevic
Ivan
I
Department of Medicine, Institute of Clinical Sciences Lund University, Lund, Sweden. ivan.dimitrijevic@med.lu.se
Andersson
Christina
C
Rissler
Pehr
P
Edvinsson
Lars
L
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D013700:Giant Cell Arteritis / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism*; D013699:Temporal Arteries / Q000378:metabolism*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D002097:C-Reactive Protein