Plasma homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in patients with rheumatoid arthritis: Is homoarginine a cardiovascular corrective in rheumatoid arthritis, an anti-ADMA?

Kayaçelebi, Arslan Arinç; Pham, Vu Vi; Willers, Janina; Hahn, Andreas; Stichtenoth, Dirk O.; Jordan, Jens; Tsikas, Dimitrios

doi:10.1016/j.ijcard.2014.07.296

Cited by 15 publications

(17 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This diametric change may suggest that hArg and ADMA could act antagonistically in the cardiovascular system (Tsikas and Kayacelebi 2014). Observations from our and other groups are supportive of an antagonism between hArg and ADMA in rheumatoid arthritis (Kayacelebi et al 2014c) and in preeclampsia (Valtonen et al 2008;Khalil et al 2013). In these conditions, circulating hArg concentrations are rather elevated.…”

Section: Introductionmentioning

confidence: 52%

“…The RA patients of the verum group received a combined add-on supplementation for 12 weeks of omega-3 fatty acids, vitamins E and A, copper and selenium. The plasma hArg, Arg and ADMA concentrations of the RA patients were reported recently (Kayacelebi et al 2014c). Plasma concentrations of hArg (Kayacelebi et al 2014a) and ADMA (Tsikas et al 2003) were measured by GC-MS/MS.…”

Section: Rheumatoid Arthritis Studymentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 52%

Section: Rheumatoid Arthritis Studymentioning

confidence: 99%

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

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a previous work, we suggested that hArg and ADMA may act antagonistically in the circulation. We assume that the value of the Arg/ADMA molar ratio may reflect the resulting net effect of hArg and Arg in the vasculature (Kayacelebi et al 2014a;Tsikas and Kayacelebi 2014). The present study suggests that the higher the hArg/ ADMA ratio is, the higher is the IGF-1 and, consequently, growth.…”

Section: Discussionmentioning

confidence: 64%

“…Unlike circulating Arg, circulating ADMA is largely independent of nutritional or pharmaceutical Arg. Nevertheless, the considerably higher ADMA plasma concentrations measured in short stature children compared to those measured in healthy children with normal stature may decrease the relative bioavailability of NO (expressed as the Arg/ADMA ratio) and may attenuate the protective effect of hArg (expressed as the hArg/ADMA ratio) in the vasculature (Kayacelebi et al 2014a;Tsikas and Kayacelebi 2014).…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in short stature children without and with growth hormone deficiency: hArg and ADMA are involved differently in growth in the childhood

Langen¹,

Kayaçelebi

Beckmann

et al. 2015

Amino Acids

Self Cite

View full text Add to dashboard Cite

Adult subjects with growth hormone (GH) deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. In adults, these events are associated with elevated circulating concentrations of asymmetric dimethylarginine (ADMA) which is an endogenous inhibitor of L-arginine (Arg)-derived nitric oxide (NO). Low circulating concentrations of homoarginine (hArg) emerged as a cardiovascular risk factor. In adults, hArg seems to antagonize ADMA. In the present work, we tested the hypothesis that children with short stature without or with GHD have altered Arg/NO pathway as compared to children with normal growth. We studied 66 short stature children (38 boys, 28 girls) aged 3.5-17.3 years, who underwent the routine L-Arginine Test to diagnose presence of GHD. GHD was confirmed in 47 children (GHD group; 30 boys, 17 girls) and was absent in the remaining 19 children (non-GHD group; 8 boys, 11 girls). In addition, we investigated 24 healthy age- and gender-matched children (10 boys, 14 girls) with normal growth. In EDTA plasma samples of all children, we determined by mass spectrometry-based methods the concentrations of Arg, hArg and ADMA, and calculated the Arg/ADMA and hArg/ADMA molar ratios. With respect to these biochemical parameters, we did not find statistically significant differences between the GHD and non-GHD groups. Comparing short with normal stature children, we found small differences regarding plasma hArg concentrations [mean ± SD; median (25th-75th percentile)]: 2.06 ± 0.52 µM; 2.12 (1.74-2.36) µM vs. 1.7 ± 0.5 µM; 1.6 (1.4-1.8) µM, P < 0.001. Compared to normal stature children, short stature children had considerably higher plasma concentrations of ADMA [0.77 ± 0.15 µM; 0.77 (0.66-0.85) µM vs. 0.57 ± 0.09 µM; 0.58 (0.50-0.63) µM, P < 0.001], but not of Arg [83.3 ± 19.2 µM; 82.2 (71.9-90.3) µM vs. 86.5 ± 17.8 µM; 84.8 (77.2-94.8) µM, P = 0.336], or the hArg/ADMA ratio [2.74 ± 0.76; 2.7 (2.2-3.1) vs. 3.1 ± 1.2; 2.85 (2.42-3.66), P = 0.161. hArg in the GHD group (r = 0.41, P = 0.004) and the hArg/ADMA ratio in both groups (r = 0.44, P = 0.002 in GHD; r = 0.55, P = 0.01 in non-GHD)], but not ADMA were positively correlated with insulin-like growth factor-1 (IGF-1). hArg and hArg/ADMA differed between girls and boys in the GHD and non-GHD groups but in the normal growth group. The hArg/ADMA ratio increased with age in all groups. Our study suggests that hArg and ADMA are involved in growth in the childhood, presumably in an antagonistic manner, with ADMA slowing and hArg accelerating growth.

show abstract

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

et al. 2015

View full text Add to dashboard Cite

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: 59-3), 153 (78 %) females] and 82 controls [median age: 44 years [quartiles: 33-55, 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.

show abstract

Plasma homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in patients with rheumatoid arthritis: Is homoarginine a cardiovascular corrective in rheumatoid arthritis, an anti-ADMA?

Cited by 15 publications

References 20 publications

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

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

Homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in short stature children without and with growth hormone deficiency: hArg and ADMA are involved differently in growth in the childhood

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

Contact Info

Product

Resources

About