Symmetric dimethylarginine (SDMA) serum levels in rheumatoid arthritis: correlations with insulin resistance and disease activity scores

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• 作者：Theodoros Dimitroulas ; James Hodson ; Aamer Sandoo ; Jacqueline Smith…
• 关键词：SDMA ; ADMA ; Rheumatoid arthritis ; Insulin resistance ; Endothelial dysfunction
• 刊名：Amino Acids
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：47
• 期：9
• 页码：1995-2004
• 全文大小：475 KB
• 参考文献：Abou-Raya A, Abou-Raya S (2006) Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmun Rev 5:331-37CrossRef PubMed
  Anderssohn M, Schwedhelm E, Lüneburg N, Vasan RS, B?ger RH (2010) Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus. Diab Vasc Dis Res 7:105-18CrossRef PubMed
  Anderssohn M, McLachlan S, Lüneburg N, Robertson C, Schwedhelm E, Williamson RM, Strachan MW, Ajjan R, Grant PJ, B?ger RH, Price JF (2014) Genetic and environmental determinants of dimethylarginines and association with cardiovascular disease in patients with type 2 diabetes. Diabetes Care 37:846-54CrossRef PubMed
  Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315-24CrossRef PubMed
  Bland JM, Altman DG (1996) Transformations, means, and confidence intervals. BMJ Br Med J 312:1079CrossRef
  B?ger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, Schulze F, Xanthakis V, Benndorf RA, Vasan RS (2009) Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation 119:1592-600PubMed Central CrossRef PubMed
  Caplin B, Leiper J (2012) Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators? Arterioscler Thromb Vasc Biol 32:1343-353PubMed Central CrossRef PubMed
  Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ (2003) QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab 284:E804–E812CrossRef PubMed
  Chobanyan-Jürgens K, Pham VV, Stichtenoth DO, Tsikas D (2011) Elevated dimethylarginine dimethylaminohydrolase (DDAH) activity in rheumatoid arthritis and spondyloarthritis. Nitric Oxide 25:436-38CrossRef PubMed
  Chung C, Giles J, Petri M, Szklo M, Post W, Blumenthal RS, Gelber AC, Ouyang P, Jenny NS, Bathon JM (2012) Prevalence of traditional modifiable cardiovascular risk factors in patients with rheumatoid arthritis: comparison with control subjects from the multi-ethnic study of atherosclerosis. Semin Arthritis Rheum 41:535-44PubMed Central CrossRef PubMed
  da Cunha VR, Brenol CV, Brenol JC, Fuchs SC, Arlindo EM, Melo IM, Machado CA, de Castro Chaves H, Jr Xavier RM (2012) Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and is associated with disease activity. Scand J Rheumatol 41:186-91CrossRef PubMed
  Daoussis D, Panoulas VF, Antonopoulos I, John H, Toms TE, Wong P, Nightingale P, Douglas KM, Kitas GD (2010) Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis. Ann Rheum Dis 69:517-21CrossRef PubMed
  Desideri G, Ferri C (2005) Endothelial activation. Sliding door to atherosclerosis. Curr Pharm Des 11:2163-175CrossRef PubMed
  Dessein PH, Joffe BI, Stanwix AE (2003) Inflammation, insulin resistance, and aberrant lipid metabolism as cardiovascular risk factors in rheumatoid arthritis. J Rheumatol 30:1403-405PubMed
  Dimitroulas T, Sandoo A, Veldhuijzen van Zanten JJ, Smith JP, Hodson J, Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD (2013) Predictors of asymmetric dimethylarginine levels in patients with rheumatoid arthritis: the role of insulin resistance. Scand J Rheumatol 42:176-81CrossRef PubMed
  Dimitroulas T, Sandoo A, Hodson J, Smith J, Panoulas VF, Kitas GD (2014) Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis. Atherosclerosis 237:38-4CrossRef PubMed
  Ferraccioli G, Gremese E (2011) Adiposity, joint and systemic inflammation: the additional risk of having a metabolic syndrome in rheumatoid arthritis. Swiss Med Wkly 141:w13211PubMed
  González M, Flores C, Pearson JD, Casanello P, Sobrevia L (2004) Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and -2 and membrane hyperpolarization in human umbilical vein endothelial cells. Pflugers Arch 448:383-94CrossRef PubMed
  Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J (2005) Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35:8-7CrossRef PubMed
  Gore MO, Lüneburg N, Schwedhelm E, Ayers CR, Anderssohn M, Khera A, Atzler D, de Lemos JA, Grant PJ, McGuire DK, B?ger RH (2013) Symmetrical dimethylarginine predicts mortality in the general population: observations from the Dallas heart study. Arterioscler Thromb Vasc Biol 33:2682-688CrossRef PubMed
  Karbach S, Wenzel P, Waisman A, Münzel T, Daiber A (2014) eNOS uncoupling in cardiovascular diseases—the role of oxidative stress and inflammation. Curr Pharm Des 20:357
• 作者单位：Theodoros Dimitroulas (1)
  James Hodson (2)
  Aamer Sandoo (1) (3)
  Jacqueline Smith (1)
  George D. Kitas (1) (4)
  
  1. Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, DY1 2HQ, UK
  2. Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2WB, UK
  3. School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, LL57 2PZ, Wales, UK
  4. Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

Vascular abnormalities predisposing to atherosclerosis are present in patients with rheumatoid arthritis (RA) and associate with excess cardiovascular risk. Symmetric dimethylarginine (SDMA), an endogenous inhibitor of nitric oxide (NO) synthase activity, has been recognised as novel risk factor for endothelial dysfunction and cardiovascular disease. We aimed to compare SDMA levels in RA patients and controls and to investigate whether they are influenced by demographic, inflammatory or metabolic factors. Serum SDMA levels were measured in 197 RA individuals [median age: 67 years (quartiles: 59-), 153 (78 %) females] and 82 controls [median age: 44 years [quartiles: 33-5, 50 (61 %) females]. Routine biochemistry tests, lipid profile, glycemic profile [glucose, insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)], as well as inflammatory markers were measured in all patients. Paired analysis was employed for the comparison of SDMA in two groups and multivariable regression models were performed to identify predictors of SDMA in the RA cohort. SDMA was significantly lower in RA than control patients in both unpaired and paired analyses (P < 0.001 and P = 0.005, respectively), with the magnitude of the difference being similar in both models. QUICKI (P = 0.005) and disease activity score-28 (P = 0.007) were positively related to SDMA in the RA cohort, whilst a negative correlation with renal function (eGFR) was detected (P = 0.005). The molecular explanation of lower serum SDMA is unclear, but the established relationships with indices of disease activity and insulin resistance, may underline the pathogenetic role of the l-arginine/NO pathway dysregulation in the development of atherosclerosis in RA. The biological and clinical importance of SDMA in RA remains to be evaluated in clinical and experimental studies. Keywords SDMA ADMA Rheumatoid arthritis Insulin resistance Endothelial dysfunction