High-throughput liquid chromatographic-tandem mass spectrometric determination of arginine and dimethylated arginine derivatives in human and mouse plasma

Schwedhelm, Edzard; Maas, Renke; Tan-Andresen, Jing; Schulze, Friedrich; Riederer, Ulrich; Böger, Rainer H.

doi:10.1016/j.jchromb.2006.11.052

Cited by 157 publications

(133 citation statements)

References 34 publications

(41 reference statements)

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“…Asymmetric dimethylarginine, symmetric dimethylarginine, and N G -monomethyl-l-arginine were determined by liquid chromatography-tandem mass spectrometry as described previously. 17 …”

Section: Measurement Of Guanidino Compoundsmentioning

confidence: 99%

Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

Choe¹,

Atzler²,

Wild³

et al. 2013

Circulation

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136

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Background— Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism with stroke pathology and outcome. Methods and Results— Increasing homoarginine levels were independently associated with a reduction in all-cause mortality in patients with ischemic stroke (7.4 years of follow-up; hazard ratio for 1-SD homoarginine, 0.79 [95% confidence interval, 0.64–0.96]; P =0.019; n=389). Homoarginine was also independently associated with the National Institutes of Health Stroke Scale+age score and 30-day mortality after ischemic stroke ( P <0.05; n=137). A genome-wide association study revealed that plasma homoarginine was strongly associated with single nucleotide polymorphisms in the l -arginine:glycine amidinotransferase ( AGAT ) gene ( P <2.1×10 −8 ; n=2806), and increased AGAT expression in a cell model was associated with increased homoarginine. Next, we used 2 genetic murine models to investigate the link between plasma homoarginine and outcome after experimental ischemic stroke: (1) an AGAT deletion (AGAT −/− ) and (2) a guanidinoacetate N -methyltransferase deletion (GAMT −/− ) causing AGAT upregulation. As suggested by the genome-wide association study, homoarginine was absent in AGAT −/− mice and increased in GAMT −/− mice. Cerebral damage and neurological deficits in experimental stroke were increased in AGAT −/− mice and attenuated by homoarginine supplementation, whereas infarct size in GAMT −/− mice was decreased compared with controls. Conclusions— Low homoarginine appears to be related to poor outcome after ischemic stroke. Further validation in future trials may lead to therapeutic adjustments of homoarginine metabolism that alleviate stroke and other vascular disorders.

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“…Asymmetric dimethylarginine, symmetric dimethylarginine, and N G -monomethyl-l-arginine were determined by liquid chromatography-tandem mass spectrometry as described previously. 17 …”

Section: Measurement Of Guanidino Compoundsmentioning

confidence: 99%

Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

Choe¹,

Atzler²,

Wild³

et al. 2013

Circulation

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136

164

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“…Mass spectrometric determinations of L-arginine, ADMA and SDMA were performed as described elsewhere by using a fully validated high throughput LC-MS/MS assay, which is commercially available (DLD Diagnostika, Hamburg, Germany). 39,40 Reactive oxygen species was measured using a spectrophotometric assay, where 1.0 mg l À1 H 2 O 2 represents one unit of reactive oxygen species. 41 Anthropometric measurements Waist circumferences, height and weight were measured according to the standard protocols.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Ethnicity-specific differences in L-arginine status in South African men

et al. 2011

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The aetiology for an increasing incidence of hypertensive cardiovascular disease amongst Africans in southern Africa is unclear. Hypertension may be induced by inadequate release of L-arginine-derived nitric oxide impairing vascular tone regulation. In addition, asymmetric dimethylarginine (ADMA) is associated with cardiovascular disease. We compared profiles of L-arginine in African and Caucasian men of similar age with cardiovascular risk factors. We studied 163 Caucasian and 132 African men, respectively, (20 to 70 years) measuring serum L-arginine, ADMA, creatinine, urea, symmetric dimethylarginine (SDMA) and blood pressure. L-arginine levels were significantly lower, whereas blood pressure and pulse wave velocity were significantly higher in African men. Simple linear regression showed ADMA more strongly associated with L-arginine in Caucasians (r ¼ 0.59 vs 0.19), whereas association of SDMA with L-arginine was significant only in Caucasians (r ¼ 0.43 vs 0.001). The stronger association of L-arginine with ADMA in Caucasian men was confirmed by multiple regression analysis (b ¼ 0.46 vs 0.25). Our findings show that the relationship of cardiovascular risk factors with serum L-arginine and some of its catabolites is different in African and Caucasian men and that this may be associated with a relatively higher prevalence of hypertension in African men.

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“…Mass spectrometric determination of ADMA and SDMA was performed as described elsewhere by using a fully validated high throughput liquid chromatography-tandem mass spectrometry (MS)/MS assay, which is commercially available (DLD Diagnostika, Hamburg, Germany) (24,25).…”

Section: Biochemical Analysesmentioning

confidence: 99%

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Schutte¹,

Schutte²,

Huisman³

et al. 2010

European Journal of Endocrinology

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Objective: Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMA's counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk. Since little information regarding ADMA or SDMA is available for Africans, our aim was to explore the relationships of ADMA and SDMA with measures of arterial stiffness and IR in Africans and Caucasians from South Africa. Methods: The study consisted of 235 nonsmoking, nondiabetic, nonobese, human immunodeficiency virus-uninfected Africans (nZ64) and Caucasians (nZ171), aged 20-70 years. We measured blood pressure, pulse wave velocity, ADMA, SDMA, and IR (homeostasis model assessment, HOMA). Results: African and Caucasian men had similar ADMA and SDMA, whereas Caucasian women had higher ADMA and SDMA than African women (P!0.05). African men and Caucasian women indicated strong correlations of ADMA with arterial stiffness (rZ0.47, PZ0.021; rZ0.26, PZ0.008), confirmed in multivariate analyses. Caucasian participants showed negative associations between SDMA and HOMA, being strongest in the men (rZK0.41; PZ0.002). Conclusion: Our results indicate that ADMA is independently associated with vascular dysfunction in African men and Caucasian women. A strong, independent negative association of SDMA with IR was found only in Caucasian participants. The molecular explanation for this is unclear, but these findings motivate experimental studies that could shed more light on these relationships.

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High-throughput liquid chromatographic-tandem mass spectrometric determination of arginine and dimethylated arginine derivatives in human and mouse plasma

Cited by 157 publications

References 34 publications

Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

Ethnicity-specific differences in L-arginine status in South African men

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

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