Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Effect of Glucocorticoids on Gelatinase (MMP-2 and MMP-9) Expression in Giant-Cell Arteritis (GCA) Using an Ex-Vivo Temporal Artery Culture Model.

Corbera-Bellalta,  Marc, Garcia-Martinez,  Ana, Planas-Rigol,  Ester, Lozano,  Ester, Segarra,  Marta, Espigol-Frigole,  Georgina, Hernandez-Rodriguez,  José

Background:

GCA is the most frequent systemic vasculitis in the elderly. Increased gelatinase expression and proteolytic activity have been demonstrated in GCA lesions. Gelatinases may play an important role in the progression of inflammatory lesions given their proinflammatory functions and elastinolytic activity and may also participate in vascular remodelling in response to injury. Glucocorticoids (GC) are the cornerstone of GCA treatment but it is not know how GC treatment influences gelatinase expression.

Purposes:

To explore the effects of GC on gelatinase expression in GCA lesions using an ex-vivo arterial culture system.

Methods:

Fresh temporal artery sections obtained from 19 GCA patients and 10 controls were embedded in the reconstituted basement membrane Matrigel™ and cultured for 5 days as described (Arthritis Rheum 2008 (suppl) 58:9; S929–S929). Cultured sections were treated with medium alone or with medium supplemented with 0.5mg/ml of dexamethasone. MMP-2 and MMP-9 mRNA was measured in recovered sections by quantitative real-time PCR (Applied Biosystems). Both gelatinases were also measured in the supernatant fluid by immunoassay (R&D Systems).

Results:

MMP-9 mRNA was significantly more abundant in cultured sections from patients compared to controls (1283±1353 vs 304±222 relative units, p=0,039). Contrarily, no differences were observed in MMP-2 mRNA between normal and GCA cultured sections (2097±918 vs 3450±2800 relative units, p=0,758). MMP-9 and MMP-2 protein concentrations were higher in the supernatant from GCA sections compared to controls (48,9±30,3 vs 7,83±7,02 ng/ml, p=0,006 for MMP-9) although differences were not significant for MMP-2 (39,1±31,5 vs 15,3±16,6 ng/ml, p=0,192). Dexamethasone treatment for 5 days highly reduced MMP-9 expression both at the mRNA (861,2±1054 vs 88±110 p=0,018) and at the protein level (48,9±30,4 vs 8,6±5,4 ng/ml, p=0,003) whereas no effect was apparent on MMP-2 expression.

Conclusion:

The pattern of gelatinase expression in cultured temporal artery sections parallels what has been observed in fresh biopsies (Ann Rheum Dis. 2007 Nov; 66(11):1429–35). In the present model, dexamethasone treatment dramatically reduced MMP9 expression with a much lesser effect on MMP-2 expression. These findings reinforce a pro-inflammatory role for MMP9 during active disease and suggest a role for MMP2 in vascular remodelling before and after treatment. Supported by SAF 05/06250 and MTV3 06/0710.

To cite this abstract, please use the following information:
Corbera-Bellalta, Marc, Garcia-Martinez, Ana, Planas-Rigol, Ester, Lozano, Ester, Segarra, Marta, Espigol-Frigole, Georgina, et al; Effect of Glucocorticoids on Gelatinase (MMP-2 and MMP-9) Expression in Giant-Cell Arteritis (GCA) Using an Ex-Vivo Temporal Artery Culture Model. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1292
DOI: 10.1002/art.29058

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