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Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study.

Abstract

Inflammation is associated with a reduced availability of NO in the vasculature. We investigated the possible involvement of altered levels of the substrate (arginine) and the inhibitor [ADMA (asymmetric ω-NG,NG-dimethylarginine)] of NOS (NO synthase). Plasma concentrations of arginine and ADMA, the inflammatory markers CRP (C-reactive protein) and MPO (myeloperoxidase), and oxLDL [oxidized LDL (low-density lipoprotein)] were measured in 369 male and 377 female participants (aged 50-87 years) of a population-based cohort study. The arginine/ADMA ratio decreased significantly across increasing tertiles of CRP and MPO. These negative associations remained significant in a linear regression model with both MPO (P = 0.002) and CRP (P < 0.001) as independent variables and adjusted for age, sex and cardiovascular risk factors. In a fully adjusted regression model, MPO was positively associated with ADMA {5.4 [95% CI (confidence interval), 1.3-9.4] nmol/l change of ADMA per S.D. increase in MPO; P = 0.010}, whereas CRP was not (P = 0.36). Conversely, in a fully adjusted model, CRP was negatively associated with arginine [-2.8 (95% CI, -4.0 to -1.6) μmol/l arginine per S.D. of CRP; P < 0.001], without a significant contribution of MPO (P = 0.23). The relationship between MPO and ADMA became stronger with increasing levels of oxLDL (1.8, 5.2 and 8.7 nmol/l ADMA per S.D. of MPO for increasing tertiles of oxLDL), consistent with the ability of MPO to amplify oxidative stress. In contrast, the relationship between CRP and arginine was not modified by levels of oxLDL. In conclusion, an unfavourable NOS substrate/inhibitor ratio may contribute to the reduced NO bioavailability associated with inflammation.

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  • Authors+Show Affiliations

    ,

    Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.

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    Source

    MeSH

    Aged
    Aged, 80 and over
    Arginine
    Biomarkers
    C-Reactive Protein
    Cohort Studies
    Female
    Humans
    Inflammation
    Lipoproteins, LDL
    Male
    Middle Aged
    Nitric Oxide Synthase
    Oxidative Stress
    Peroxidase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21306304

    Citation

    van der Zwan, Leonard P., et al. "Systemic Inflammation Is Linked to Low Arginine and High ADMA Plasma Levels Resulting in an Unfavourable NOS Substrate-to-inhibitor Ratio: the Hoorn Study." Clinical Science (London, England : 1979), vol. 121, no. 2, 2011, pp. 71-8.
    van der Zwan LP, Scheffer PG, Dekker JM, et al. Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study. Clin Sci. 2011;121(2):71-8.
    van der Zwan, L. P., Scheffer, P. G., Dekker, J. M., Stehouwer, C. D., Heine, R. J., & Teerlink, T. (2011). Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study. Clinical Science (London, England : 1979), 121(2), pp. 71-8. doi:10.1042/CS20100595.
    van der Zwan LP, et al. Systemic Inflammation Is Linked to Low Arginine and High ADMA Plasma Levels Resulting in an Unfavourable NOS Substrate-to-inhibitor Ratio: the Hoorn Study. Clin Sci. 2011;121(2):71-8. PubMed PMID: 21306304.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study. AU - van der Zwan,Leonard P, AU - Scheffer,Peter G, AU - Dekker,Jacqueline M, AU - Stehouwer,Coen D A, AU - Heine,Robert J, AU - Teerlink,Tom, PY - 2011/2/11/entrez PY - 2011/2/11/pubmed PY - 2011/6/29/medline SP - 71 EP - 8 JF - Clinical science (London, England : 1979) JO - Clin. Sci. VL - 121 IS - 2 N2 - Inflammation is associated with a reduced availability of NO in the vasculature. We investigated the possible involvement of altered levels of the substrate (arginine) and the inhibitor [ADMA (asymmetric ω-NG,NG-dimethylarginine)] of NOS (NO synthase). Plasma concentrations of arginine and ADMA, the inflammatory markers CRP (C-reactive protein) and MPO (myeloperoxidase), and oxLDL [oxidized LDL (low-density lipoprotein)] were measured in 369 male and 377 female participants (aged 50-87 years) of a population-based cohort study. The arginine/ADMA ratio decreased significantly across increasing tertiles of CRP and MPO. These negative associations remained significant in a linear regression model with both MPO (P = 0.002) and CRP (P < 0.001) as independent variables and adjusted for age, sex and cardiovascular risk factors. In a fully adjusted regression model, MPO was positively associated with ADMA {5.4 [95% CI (confidence interval), 1.3-9.4] nmol/l change of ADMA per S.D. increase in MPO; P = 0.010}, whereas CRP was not (P = 0.36). Conversely, in a fully adjusted model, CRP was negatively associated with arginine [-2.8 (95% CI, -4.0 to -1.6) μmol/l arginine per S.D. of CRP; P < 0.001], without a significant contribution of MPO (P = 0.23). The relationship between MPO and ADMA became stronger with increasing levels of oxLDL (1.8, 5.2 and 8.7 nmol/l ADMA per S.D. of MPO for increasing tertiles of oxLDL), consistent with the ability of MPO to amplify oxidative stress. In contrast, the relationship between CRP and arginine was not modified by levels of oxLDL. In conclusion, an unfavourable NOS substrate/inhibitor ratio may contribute to the reduced NO bioavailability associated with inflammation. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/21306304/Systemic_inflammation_is_linked_to_low_arginine_and_high_ADMA_plasma_levels_resulting_in_an_unfavourable_NOS_substrate_to_inhibitor_ratio:_the_Hoorn_Study_ L2 - http://clinsci.org/cgi/pmidlookup?view=long&amp;pmid=21306304 DB - PRIME DP - Unbound Medicine ER -