Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study.
ADMA
Endothelial dysfunction
Flow-mediated pulse amplitude tonometry
Rheumatoid arthritis
SDMA
l-Homoarginine
Journal
Microvascular research
ISSN: 1095-9319
Titre abrégé: Microvasc Res
Pays: United States
ID NLM: 0165035
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
19
03
2020
revised:
27
06
2020
accepted:
27
06
2020
pubmed:
6
7
2020
medline:
26
11
2020
entrez:
6
7
2020
Statut:
ppublish
Résumé
The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known. l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses. Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]. ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group.
Sections du résumé
BACKGROUND
The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known.
METHODS
l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses.
RESULTS
Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032].
CONCLUSIONS
ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group.
Identifiants
pubmed: 32622695
pii: S0026-2862(20)30098-4
doi: 10.1016/j.mvr.2020.104038
pii:
doi:
Substances chimiques
Biomarkers
0
Homoarginine
156-86-5
Citrulline
29VT07BGDA
symmetric dimethylarginine
49787G1ULV
N,N-dimethylarginine
63CV1GEK3Y
Arginine
94ZLA3W45F
Banques de données
ClinicalTrials.gov
['NCT02341066']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104038Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.