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The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study

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Abstract

Introduction/objectives

Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) — a biomarker of atherosclerosis — and assessments of macrovascular endothelial function in patients with SSc.

Methods

This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT).

Results

Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc.

Conclusions

The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease.

Key Points

• ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc.

•ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study.

•The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.

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Abbreviations

ADMA:

Asymmetrical dimethylarginine

SSc:

Systemic sclerosis

cIMT:

Carotid intima-media thickness

ACA:

Anti-centromeric antibodies

SCL-70:

Anti-topoisomerase IIa

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Authors and Affiliations

  1. Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Konstantinoupoleos Str. 49, Thessaloniki, Greece

    Eleni Pagkopoulou, Alexandros Garyfallos & Theodoros Dimitroulas

  2. First Department of Cardiology, Hippokration Hospital, Medical School of Athens University, Athens, Greece

    Stergios Soulaidopoulos

  3. Second Propedeutic Department of Internal Medicine, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Niki Katsiki, Asterios Karagiannis & Michael Doumas

  4. International Hellenic University, Thessaloniki, Greece

    Afroditi Malliari & Charalampos Loutradis

  5. Evangelismos Hemodialysis Unit, Veria, Greece

    Charalampos Loutradis

  6. Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, UK

    George Kitas

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  1. Eleni Pagkopoulou
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Pagkopoulou, E., Soulaidopoulos, S., Katsiki, N. et al. The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study. Clin Rheumatol 42, 1077–1085 (2023). https://doi.org/10.1007/s10067-022-06472-w

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