Increased angiotensin II type 1 receptor expression in temporal arteries from patients with giant cell arteritis.
OBJECTIVE
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 (AT(1)) and type 2 (AT(2)) receptors in GCA.


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


METHODS
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-AT(1) and anti-AT(2) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries.


METHODS
AT(1) and AT(2) 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. AT(1) 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 AT(1) receptor immunostaining of both vascular smooth muscle cells and infiltrating inflammatory cells. Only faint immunostaining was seen for AT(2) receptors, primarily in the endothelial cells, and to a lesser extent on the smooth muscle cells. Immunostaining with antibodies for the AT(2) receptor was similar in the patients with GCA and in controls.


CONCLUSIONS
These results suggest that AT(1) 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.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Department of Emergency Medicine, Division of Experimental Vascular Research, Clinical Sciences, Lund University, Lund, Sweden. ivan.dimitrijevic@med.lu.se
Ivan
I
Dimitrijevic
Malin
M
Malmsjö
Christina
C
Andersson
Pehr
P
Rissler
Lars
L
Edvinsson
D000368:Aged; D000369:Aged, 80 and over; D004730:Endothelium, Vascular / 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; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012189:Retrospective Studies; D013699:Temporal Arteries / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2