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

Kruszelnicka, Olga; Chyrchel, Bernadeta; Golay, Alain; Surdacki, Andrzej

doi:10.1007/s00726-015-1976-3

Cited by 19 publications

(16 citation statements)

References 66 publications

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“…Whether the beneficial effects of the combined treatment seen in this are due to an improvement of the L-Arg/NO pathway and are mediated by l-arginine, metformin or both remains to be investigated. It is worth mentioning that metformin administration (1655 mg/d) may enhance ADMA synthesis, but decrease plasma-soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients suffering from type 2 diabetes mellitus and stable coronary artery disease (Kruszelnicka et al 2015).…”

Section: Effect Of Steroid and Creatine Medicationmentioning

confidence: 99%

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

et al. 2015

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The L-arginine/nitric oxide (L-Arg/NO) pathway regulates endothelial function and may play an important role in the pathogenesis of Duchenne muscular dystrophy (DMD). Yet, this pathway is poorly investigated in children suffering from DMD. Endothelial dysfunction can affect the perfusion of contracting muscles, thus leading to ischemia and hypoxia. In the present study, we tested the hypothesis that reduced NO production due to elevated synthesis of N (G),N (G)-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA), an endogenous inhibitor of NO synthesis, is a possible pathophysiological mechanism for progressive intramuscular muscle ischemia and disturbed endothelial function in children with DMD. Given the possible antagonistic action of homoarginine (hArg) on ADMA, we also analyzed this amino acid. We investigated 55 male patients with DMD and 54 healthy male controls (HC; aged 11.9 ± 4.8 vs. 11.1 ± 4.9 years, mean ± SD). Urinary creatinine and metabolites of the L-Arg/NO pathway were measured in plasma and urine by GC-MS or GC-MS/MS. Urine levels of ADMA and its major urinary metabolite dimethylamine (DMA), nitrite and nitrate (P < 0.001 for all) and hArg (P = 0.002) were significantly higher in DMD patients compared to HC, while the urinary DMA/ADMA molar ratio was lower (P = 0.002). In plasma, nitrate (P < 0.001), hArg (P = 0.002) and the hArg/ADMA ratio (P < 0.001) were lower in DMD than in HC. In plasma, ADMA (631 ± 119 vs. 595 ± 129 nM, P = 0.149), arginine and nitrite did not differ between DMD and HC. In DMD, positive correlations between ADMA, DMA or nitrate excretion and the stage of disease (according to Vignos and Thompson) were found. In DMD patients on steroid medication, lower concentrations of ADMA in plasma, and of DMA, ADMA, nitrate and hArg in urine were observed compared to non-treated patients. The L-Arg/NO pathway is impaired in DMD patients, with the disease progression being clinically negatively correlated with the extent of impairment. One of the underlying mechanisms in DMD may involve insufficient antagonism of ADMA by hArg. Steroids, but not creatine supplementation, seems to improve the L-Arg/NO pathway in DMD.

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Section: Effect Of Steroid and Creatine Medicationmentioning

confidence: 99%

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

et al. 2015

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“…VCAM-1 is an inflammatory protein that is up-regulated in preeclampsia and associated with endothelial dysfunction. 61 Metformin previously has been shown to reduce endothelial cell inflammatory gene and protein expression 83,84 and serum VCAM-1 concentrations in patients with diabetes mellitus 59 and impaired glucose tolerance. 60 We demonstrated that, in the presence of TNFa that is an inflammatory cytokine that is up-regulated in preeclampsia, 76 metformin reduced VCAM-1 expression in endothelial cells.…”

Section: Metformin Rescues Endothelial Dysfunction and Impaired Vasodmentioning

confidence: 99%

“…Metformin has been reported to have vasoprotective properties; epidemiologic studies have shown that it reduces cardiovascular morbidity in patients with polycystic ovarian syndrome 26 and diabetes mellitus. 57,58 This has been attributed to its ability to reduce vascular cell adhesion molecule 1 (VCAM-1), 59,60 which is a molecule that is expressed on the luminal surface of blood vessels in the presence of inflammation and is increased in preeclampsia. 61 Metformin has also been reported to induce vasodilation of diabetic rat vessels.…”

Section: Introductionmentioning

confidence: 99%

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction

Brownfoot

Hastie

Hannan

et al. 2016

American Journal of Obstetrics and Gynecology

184

154

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Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain. The activity of the mitochondrial electron transport chain was increased in preterm preeclamptic placenta. Metformin reduced endothelial dysfunction, enhanced vasodilation in omental arteries, and induced angiogenesis. Metformin has potential to prevent or treat preeclampsia.

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“…Moreover, the ADMA levels were similar among patients with no difference in their glycemic control receiving either metformin either repaglinide [257]. Worth noting, a study among patients with diabetes mellitus type 2 and stable coronary artery disease revealed that patients receiving metformin have higher circulating ADMA levels as compared to subjects not receiving metformin [258]. Therefore, it remains obscure whether metformin actually exerts part of its beneficial action via regulation of ADMA.…”

Section: Blood Glucose Lowering Medicationsmentioning

confidence: 98%

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic Approaches

Tousoulis

Georgakis²,

Oikonomou³

et al. 2015

CMC

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Asymmetric dimethylarginine (ADMA) is a competitive endogenous inhibitor of nitric oxide synthase with a key role in the pathophysiology of endothelial dysfunction, in the progression of atherosclerosis and in cardiovascular diseases. Statins, renin-angiotensin-aldosterone system inhibitors, blood glucose lowering agents, insulin sensitizers, beta-blockers, estrogen replacement therapy, antioxidants, complex B vitamins, L-arginine and acetylsalicylic acid have been evaluated for their ability to reduce ADMA levels or inhibit its actions. Despite the major beneficial effects of these agents in cardiovascular disease, research has shown that their favorable actions are only partially mediated by reducing ADMA levels or by bypassing its effect in nitric oxide synthesis. Novel therapeutic approaches targeting selectively ADMA are encouraging, but have only been tested in vitro or in animal studies and further research is needed in order to conclude on how therapeutic strategies modulating ADMA actions can affect atherosclerosis progression and cardiovascular diseases.

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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

Cited by 19 publications

References 66 publications

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic Approaches

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