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Association of Asymmetric and Symmetric Dimethylarginine with Inflammation in the Population-Based Study of Health in Pomerania

Affiliation
Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, 37075 Göttingen, Germany
Winkler, Martin Sebastian;
ORCID
0000-0002-2016-5852
Affiliation
Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany
Bahls, Martin;
ORCID
0000-0003-3770-5357
Affiliation
Institute of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany(E.S.)
Böger, Rainer H.;
ORCID
0000-0002-0154-7353
Affiliation
German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany
Ittermann, Till;
ORCID
0000-0001-7471-475X
Affiliation
Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany
Dörr, Marcus;
Affiliation
German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany
Friedrich, Nele;
ORCID
0000-0003-3597-6276
Affiliation
Institute of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany(E.S.)
Schwedhelm, Edzard

The amino acids arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are related to nitric oxide (NO) metabolism and potential markers of two different disease entities: cardiovascular disease such as atherosclerosis and systemic inflammation in critically ill patients with sepsis. Although very different in their pathophysiological genesis, both entities involve the functional integrity of blood vessels. In this context, large population-based data associating NO metabolites with proinflammatory markers, e.g., white blood cell count (WBC), high-sensitivity C-reactive protein (hsCRP), and fibrinogen, or cytokines are sparse. We investigated the association of Arg, ADMA and SDMA with WBC, hsCRP, and fibrinogen in 3556 participants of the Study of Health in Pomerania (SHIP)-TREND study. Furthermore, in a subcohort of 456 subjects, 31 inflammatory markers and cytokines were analyzed. We identified Arg and SDMA to be positively associated with hsCRP (β coefficient 0.010, standard error (SE) 0.002 and 0.298, 0.137, respectively) as well as fibrinogen (β 5.23 × 10 −3 , SE 4.75 × 10 −4 and 0.083, 0.031, respectively). ADMA was not associated with WBC, hsCRP, or fibrinogen. Furthermore, in the subcohort, Arg was inversely related to a proliferation-inducing ligand (APRIL). SDMA was positively associated with osteocalcin, tumor necrosis factor receptor 1 and 2, and soluble cluster of differentiation 30. Our findings provide new insights into the involvement of Arg, ADMA, and SDMA in subclinical inflammation in the general population.

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