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Rheumatology Advance Access originally published online on August 27, 2008
Rheumatology 2008 47(11):1682-1685; doi:10.1093/rheumatology/ken346
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Asymmetrical dimethylarginine in systemic sclerosis-related pulmonary arterial hypertension

T. Dimitroulas1, G. Giannakoulas2, T. Sfetsios1, H. Karvounis2, H. Dimitroula2, G. Koliakos3 and L. Settas1

1First Department of Internal Medicine, 2First Department of Cardiology, AHEPA University Hospital and 3Department of Biochemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Correspondence to: T. Dimitroulas, First Department of Internal Medicine, AHEPA University Hospital, Stilp. Kiriakidi 1, Thessaloniki 54636, Greece. E-mail: dimitroul{at}hotmail.com


   Abstract

Objectives. SSc is a CTD characterized by vascular involvement, with generalized disturbance of the microcirculation, which may lead to pulmonary artery hypertension (PAH). Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor. Increased concentrations of plasma ADMA may also contribute to endothelial dysfunction in patients with pulmonary vascular disease. The aim of our study was to elucidate the possible relationship between serum ADMA and PAH in patients with SSc. Moreover, we sought to investigate the effect of ADMA levels on the functional capacity of these patients.

Methods. Plasma ADMA levels were measured in 66 patients with SSc (63 females, mean age 57.8 ± 12.8 yrs, median duration of disease 9.9 yrs, 47 with lcSSc and 19 with dcSSc disease) and 30 healthy controls (29 females, mean age 58.2 ± 8.4 yrs). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, lung function tests, 6-min walk test (6MWT) and serum ADMA levels were recorded from patients.

Results. In 24 patients, the diagnosis of PAH was established. Mean value of ADMA for SScPAH patients was 0.44 ± 0.22 µmol/l compared with 0.26 ± 0.18 µmol/l for patients without PAH and 0.25 ± 0.20 µmol/l for controls (P = 0.001). ADMA levels were inversely correlated with the 6MWT (r = –0.55, P = 0.005).

Conclusions. In patients with SScPAH, increased ADMA serum levels and their negative association with exercise capacity suggests that the NO pathway is involved in the development of pulmonary vascular disease.

KEY WORDS: Scleroderma and related disorders, Biochemistry, Biomarkers, Ultrasonography

Submitted 20 March 2008; revised version accepted 22 July 2008.
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