Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease

Abstract

Elevated circulating concentrations of total l-homocysteine (thCys) and free asymmetric dimethylarginine (ADMA) are long-established cardiovascular risk factors. Low circulating l-homoarginine (hArg) concentrations were recently found to be associated with increased cardiovascular morbidity and mortality. The biochemical pathways of these amino acids overlap and share the same cofactor S-adenosylmethionine (SAM). In the present study, we investigated potential associations between hArg, l-arginine (Arg), ADMA and thCys in plasma of patients suffering from rheumatoid arthritis (RA), coronary artery disease (CAD) or peripheral artery occlusive disease (PAOD). In RA, we did not find any correlation between ADMA or hArg and thCys at baseline (n = 100) and after (n = 83) combined add-on supplementation of omega-3 fatty acids, vitamin E, vitamin A, copper, and selenium, or placebo (soy oil). ADMA correlated with Arg at baseline (r = 0.446, P < 0.001) and after treatment (r = 0.246, P = 0.03). hArg did not correlate with ADMA, but correlated with Arg before (r = 0.240, P = 0.02) and after treatment (r = 0.233, P = 0.03). These results suggest that hArg, ADMA and Arg are biochemically familiar with each other, but unrelated to hCys in RA. In PAOD and CAD, ADMA and thCys did not correlate.

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Abbreviations

ADMA:

Asymmetric dimethylarginine (N G,N G-dimethyl-l-arginine)

AGAT:

Arginine:glycine amidinotransferase

CAD:

Coronary artery disease

GAMT:

Guanidinoacetate methyltransferase

GC–MS:

Gas chromatography–mass spectrometry

GC–MS/MS:

Gas chromatography–tandem mass spectrometry

hArg:

Homoarginine

hCys/thCys:

Homocysteine/total homocysteine

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PAOD:

Peripheral arterial occlusive disease

RA:

Rheumatoid arthritis

SAH:

S-Adenosylhomocysteine hydrolase

SAM:

S-adenosylmethionine

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Acknowledgments

The authors are thankful to Bibiana Beckmann for excellent laboratory assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Dimitrios Tsikas.

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Kayacelebi, A.A., Willers, J., Pham, V.V. et al. Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease. Amino Acids 47, 1885–1891 (2015). https://doi.org/10.1007/s00726-015-1915-3

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Keywords

  • Cardiovascular risk
  • Homoarginine
  • Homocysteine
  • Methylation
  • Plasma
  • Rheumatoid arthritis