Interaction of the cardiovascular risk marker asymmetric dimethylarginine (ADMA) with the human cationic amino acid transporter 1 (CAT1)

Strobel, Joachim; Mieth, Maren; Endreß, Beate; Auge, Daniel; König, Jörg; Fromm, Martin F.; Maas, Renke

doi:10.1016/j.yjmcc.2012.06.002

Cited by 57 publications

(69 citation statements)

References 66 publications

(76 reference statements)

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“…In vitro studies have also shown SDMA to activate monocytes, resulting in increased IL-6 and TNFα production, as well as increased reactive oxygen species generation [26,27]. SDMA, unlike ADMA, is not a potent NO synthase inhibitor, but appears to inhibit intracellular arginine transport, and thus may limit arginine availability for NO synthesis [28]. Therefore, one might expect to observe plasma SDMA concentrations correlating directly with platelet aggregability.…”

Section: Discussionmentioning

confidence: 99%

Platelet hyperaggregability in patients with atrial fibrillation

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Ball

Ngo

et al. 2015

Herz

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Section: Discussionmentioning

confidence: 99%

Platelet hyperaggregability in patients with atrial fibrillation

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et al. 2015

Herz

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“…Of note, metformin pretreatment attenuated liver damage, reduced hepatic ADMA content but increased plasma ADMA in experimental inflammatory liver injury, which can indicate the importance of an asymmetrical distribution of ADMA between the tissue and plasma (Bal et al 2014). However, although ADMA at equimolar concentrations reduced the uptake of radiolabeled metformin by Xenopus laevis oocytes (Detaille et al 2002), even a threefold excess of metformin did not affect cellular uptake of l-arginine by the cationic amino acid transporter-1, known to transport also ADMA, in human embryonic kidney cells (Strobel et al 2012).…”

Section: Mechanistic Considerationsmentioning

confidence: 89%

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

et al. 2015

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Metformin, the drug of first choice in type 2 diabetes mellitus (T2DM), reduces cardiovascular (CV) morbidity and mortality in part independently of improved glycemic control and changes in traditional risk factors. However, there are discordant reports on the effects of metformin on endothelial function in T2DM. Our aim was to compare biochemical endothelial markers in patients with stable coronary artery disease (CAD) and T2DM stratified by metformin use. We studied 70 patients (29 women, age 68 ± 9 years) with established T2DM referred for elective coronary angiography owing to stable angina who were receiving a standard CV medication and metformin or other oral antidiabetic drugs. Exclusion criteria included heart failure and other relevant coexistent disorders. Biochemical indices of endothelial dysfunction and activation at admission were compared according to metformin use for at least 1 year prior to index hospitalization. Clinical characteristics were similar in patients receiving metformin (n = 40) vs. those on other oral antidiabetic agents (n = 30). Plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) was lower (553 ± 148 vs. 668 ± 170 µg/L, P = 0.004) and asymmetric dimethylarginine (ADMA) higher (0.53 ± 0.09 vs. 0.48 ± 0.08 µM, P = 0.01) in subjects on metformin, which was maintained in multivariate analysis. Symmetric dimethylarginine, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and E-selectin did not differ across the groups. The results were substantially unchanged after exclusion of insulin users. Thus, metformin use appears differentially associated with sVCAM-1 and ADMA in patients with T2DM and stable CAD. Whether this observation may reflect different prognostic effects of these endothelial markers in diabetes remains to be studied.

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“…The plasma levels of ADMA and SDMA are affected by several overlapping as well as distinct metabolic pathways. [3,4,[85][86][87][88][89][90] Elevation of ADMA may predominantly represent impaired dimethylarginine dimethylaminohydrolase (DDAH) activity [4] while elevation of SDMA more likely reflects impaired renal function [91,92] and/or impaired alanine-glyoxylate aminotransferase 2 (AGXT2) activity (i.e. hyper beta-aminoisobutyric acid uria).…”

Section: Adma and Sdma Levels And Risk Prediction And Clinical Utilitymentioning

confidence: 99%

“…• Inhibition of nitric oxide synthases (eNOS, nNOS and iNOS) [2,3] • Weak inhibition of L-arginine transport [88] • Activation of NF-κB with enhanced expression of inflammatory cytokines [95] • …”

Section: Renal Excretionmentioning

confidence: 99%