ArticleArthritis research & therapy2018
Elevated levels of plasma symmetric dimethylarginine and increased arginase activity as potential indicators of cardiovascular comorbidity in rheumatoid arthritis.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Accelerated atherosclerosis in rheumatoid arthritis: a systematic review.F1000Research · 2022Pooled it
- Asymmetric and symmetric dimethylarginine concentration as an indicator of cardiovascular diseases in rheumatoid arthritis patients: a systematic review and meta-analysis of case-control studies.Clinical rheumatology · 2020Pooled it
- A Longitudinal Study Reveals Metabolomic Markers for Individuals at Risk, Disease Severity, and Treatment Response in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeted metabolomic evaluation of peripheral blood mononucleated cells from patients with PMM2-CDG.Scientific reports · 2025Article
- SDMA as a marker and mediator in cerebrovascular disease.Clinical science (London, England : 1979) · 2024Review
- Advancing Basic and Translational Science: Highlights From the Basic Science Workshop at the GRAPPA 2023 Annual Meeting.The Journal of rheumatology · 2024Article
- High fat diet increases the severity of collagen-induced arthritis in mice by altering the gut microbial community.Advances in rheumatology (London, England) · 2024Article
- Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.Biomedicines · 2024Article
- Arsenic Exposure-Related Hypertension in Bangladesh and Reduced Circulating Nitric Oxide Bioavailability.Environmental health perspectives · 2024Article
- Red blood cell-derived arginase release in hemolytic uremic syndrome.Journal of translational medicine · 2024Article
- L-arginine metabolism inhibits arthritis and inflammatory bone loss.Annals of the rheumatic diseases · 2024Article
- Arginine Dysregulation and Myocardial Dysfunction in a Mouse Model and Children with Chronic Kidney Disease.Nutrients · 2023Article
- Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?Current issues in molecular biology · 2023Review
- Article
- Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients.International journal of molecular sciences · 2023Article
- TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis.Journal of clinical medicine · 2022Article
- Metabolic Profiling in Rheumatoid Arthritis, Psoriatic Arthritis, and Psoriasis: Elucidating Pathogenesis, Improving Diagnosis, and Monitoring Disease Activity.Journal of personalized medicine · 2022Review
- A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities.Metabolites · 2022Review
- Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment.Scientific reports · 2022Article
- The Influence of Arginine Methylation in Immunity and Inflammation.Journal of inflammation research · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRheumatoid arthritis (RA) patients are at high risk of developing cardiovascular disease (CVD). In RA, chronic inflammation may lead to endothelial dysfunction, an early indicator of CVD, owing to diminished nitric oxide (NO) production. Because L-arginine is the sole precursor of NO, we hypothesized that levels of L-arginine metabolic products reflecting NO metabolism are altered in patients with RA.
methodsPlasma samples from patients with RA (n = 119) and age- and sex-matched control subjects (n = 238) were used for this study. Using LC-MS/MS, we measured plasma levels of free L-arginine, L-ornithine, L-citrulline, L-N
resultsCompared with healthy control subjects, the RA cohort showed significantly lower levels of plasma L-arginine (46.11 ± 17.29 vs. 74.2 ± 22.53 μmol/L, p < 0.001) and GABR (0.36 ± 0.16 vs. 0.73 ± 0.24, p < 0.001), elevated levels of ADMA (0.76 ± 0.12 vs. 0.62 ± 0.12 μmol/L, p < 0.001), SDMA (0.54 ± 0.14 vs. 0.47 ± 0.13 μmol/L, p < 0.001), and ArgMI (6.51 ± 1.86 vs. 5.54 ± 1.51, p < 0.001). We found an approximately fourfold increase in arginase activity (33.8 ± 1.1 vs. 8.4 ± 0.8 U/L, p < 0.001), as well as elevated levels of arginase-mediated L-arginine catalytic product L-ornithine (108.64 ± 30.26 vs. 69.3 ± 20.71 μmol/L, p < 0.001), whereas a nitric oxide synthase (NOS) catalytic product, the L-citrulline level, was diminished in RA (30.32 ± 9.93 vs. 36.17 ± 11.64 μmol/L, p < 0.001). Patients with RA with existing CVD had higher arginase activity than patients with RA without CVD (p = 0.048).
conclusionsGlobal L-arginine bioavailability was diminished, whereas plasma arginase activity, ADMA, and SDMA levels were elevated, in patients with RA compared with healthy control subjects. Plasma SDMA was associated with hypertension and hyperlipidemia in patients with RA. This dysregulated L-arginine metabolism may function as a potential indicator of CVD risk in patients with RA.
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