Increased Angiotensin II Type 1 Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis
Received 19 June 2008; received in revised form 12 October 2008; accepted 5 December 2008.
Purpose
Currently, giant cell arteritis (GCA) is primarily treated with corticosteroids or immunomodulating agents, but there is interest in identifying other noncorticosteroid alternatives. Similarities exist in the injury pathways between GCA and atherosclerosis. Angiotensin II is a vasoactive peptide involved in vessel inflammation during atherosclerosis, and angiotensin II receptor inhibitors are effective in preventing atherosclerosis. The present study was performed to elucidate the role of angiotensin type 1 (AT1) and type 2 (AT2) receptors in GCA.
Design
Experimental retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue.
Participants
Ten patients with GCA and 10 control patients, who were clinically suspected of having GCA but were diagnosed as not having GCA, were included.
Methods
Immunohistochemistry, using anti-AT1 and anti-AT2 antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries.
Main Outcome Measures
AT1 and AT2 receptor immunostaining intensity was quantified.
Results
Hematoxylin-eosin–stained sections of temporal arteries from patients with GCA showed intimal hyperplasia, internal elastic lamina degeneration, and band-shaped infiltrates of inflammatory cells, including lymphocytes, histocytes, and multinucleated giant cells. AT1 receptor staining was primarily observed in the medial layer of the temporal arteries and was higher in the patients with GCA than in the control patients. This was a result of increased AT1 receptor immunostaining of both vascular smooth muscle cells and infiltrating inflammatory cells. Only faint immunostaining was seen for AT2 receptors, primarily in the endothelial cells, and to a lesser extent on the smooth muscle cells. Immunostaining with antibodies for the AT2 receptor was similar in the patients with GCA and in controls.
Conclusions
These results suggest that AT1 receptors play a role in the development of GCA. Inhibition of the angiotensin system may thus provide a noncorticosteroid alternative for the treatment of GCA.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
1Department of Emergency Medicine, Clinical Sciences, Lund University, Lund, Sweden
2Department of Ophthalmology, Clinical Sciences, Lund University, Lund, Sweden
3Department of Pathology, Clinical Sciences, Lund University, Lund, Sweden
Correspondence: Ivan Dimitrijevic, MD, Division of Experimental Vascular Research, BMC A13, SE-221 84 Lund, Sweden
Manuscript no. 2008-748.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Supported by the Swedish Research Council and the Heart and Lung Foundation (Sweden).
ABSTRACT