Asymmetrical dimethylarginine: A novel risk factor for coronary artery disease

Lu, Tse‐Min; Ding, Yu‐An; Charng, Min‐Ji; Lin, Shing‐Jong

doi:10.1002/clc.4960261006

Cited by 74 publications

(51 citation statements)

References 38 publications

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“…Increased ADMA, an endogenous inhibitor of nitric oxide synthase, has been observed in subjects with cardiovascular disease (CVD) [1][2][3], where it results in reduced nitric oxide bioavailability, leading to endothelial dysfunction and CVD [4,5]. Therapies that lower ADMA and reduce endothelial dysfunction may therefore reduce CVD risk.…”

Section: Introductionmentioning

confidence: 99%

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

et al. 2010

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Woodside, J. (2010). Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and Creactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial. European Journal of Nutrition, 49(8) AbstractPurpose Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels. Methods A randomised, double-blind, factorial design, intervention study was carried out on 132 men with mildly elevated homocysteine levels, allocated to four groups (a) B vitamins alone-1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin daily, (b) antioxidants alone-150 mg ascorbic acid, 67 mg vitamin E, 9 mg b-carotene daily, (c) B vitamins with antioxidant vitamins, or (d) placebo. A total of 101 men completed the study to 8 weeks.Results When the percentage of baseline ADMA and CRP was examined at 8 weeks, no statistically significant differences were observed between the four groups (p = 0.21 and p = 0.90, respectively). Similar non-significant results were observed when analysis was stratified based on baseline CRP levels (\1.0 mg/L, p = 0.10; C1.0 mg/L, p = 0.64) and smoking status (all p C 0.05). Conclusions Supplementation with moderate doses of B vitamins and/or antioxidants did not alter either ADMA or CRP concentrations in these middle-aged, apparently healthy men with mildly elevated homocysteine levels.

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Section: Introductionmentioning

confidence: 99%

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

et al. 2010

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“…Several factors have been suggested to contribute to endothelial dysfunction, such as decreased activity and/or expression of endothelial nitric oxide synthase and/or increased vascular formation of oxygen-derived free radicals (2,3). Asymmetric dimethylarginine (ADMA) 2 is an endogenously synthesized inhibitor of NOS that has been gaining increased attention in the cardiovascular field (2, 4 -9). In the heart, ADMA and other NOS inhibitors cause reduced heart rate and cardiac output (10,11).…”

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Redox Control of Protein Arginine Methyltransferase 1 (PRMT1) Activity

Morales

Nitzel

Price

et al. 2015

Journal of Biological Chemistry

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“…Several potential causes of NO deficiency in disease settings have been proposed. Among these, high circulating levels of the endogenous methylarginine NOS inhibitor asymmetric dimethylarginine (ADMA) has been hypothesized to be of particular importance (15)(16)(17)(18)(19)(20)(21). In neurons and the brain, it has been shown that the methyl arginine L-NMMA is also present, however, the levels of this methylarginine have not been previously considered in studies evaluating vascular dysfunction (22).…”

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confidence: 99%

Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function

Cardounel

Cui

Samouilov

et al. 2007

Journal of Biological Chemistry

221

172

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In endothelium, NO is derived from endothelial NO synthase (eNOS)-mediated L-arginine oxidation. Endogenous guanidinomethylated arginines (MAs), including asymmetric dimethylarginine (ADMA) and N G -methyl-L-arginine (L-NMMA), are released in cells upon protein degradation and are competitive inhibitors of eNOS. However, it is unknown whether intracellular MA concentrations reach levels sufficient to regulate endothelial NO production. Therefore, the dose-dependent effects of ADMA and L-NMMA on eNOS function were determined. Kinetic studies demonstrated that the K m for L-arginine is 3.14 M with a V max of 0.14 mol mg The biological significance of guanidino-methylated arginine derivatives has been known since the inhibitory actions of N G -methyl-L-arginine (L-NMMA) 3 on macrophage induced cytotoxicity were first demonstrated. It was subsequently realized that these effects were mediated through inhibition of NO release (1). NO has been demonstrated as a critical effector molecule in the maintenance of vascular function (2-4). In the vasculature, NO is derived from the oxidation of L-Arg, catalyzed by the constitutively expressed enzyme, eNOS (5-7). This endothelial-derived NO diffuses from the vascular endothelium into the smooth muscle cell layer where it activates soluble guanylate cyclase leading to smooth muscle relaxation (2-4). In addition to its role in the maintenance of vascular tone, NO helps to maintain the anti-atherogenic character of the normal vascular wall. NO, in concert with various cell signaling molecules, has been demonstrated to maintain smooth muscle cell quiescence and as such, counteracts pro-proliferative agents, specifically those involved in the propagation of athero-proliferative disorders (8 -14). As such, eNOS dysfunction is an early symptom of vascular disease and is manifested through insufficient NO bioavailability. Several potential causes of NO deficiency in disease settings have been proposed. Among these, high circulating levels of the endogenous methylarginine NOS inhibitor asymmetric dimethylarginine (ADMA) has been hypothesized to be of particular importance (15)(16)(17)(18)(19)(20)(21). In neurons and the brain, it has been shown that the methyl arginine L-NMMA is also present, however, the levels of this methylarginine have not been previously considered in studies evaluating vascular dysfunction (22).ADMA and L-NMMA are endogenous inhibitors of NOS and are derived from the proteolysis of methylated arginine residues on various proteins. The methylation is carried out by a group of enzymes referred to as protein-arginine methyltransferase (23). Subsequent proteolysis of proteins containing methylarginine groups leads to the release of free methylarginine into the cytoplasm, and if sufficient levels are reached NO production from NOS would be inhibited (24, 25). To date, six different isoforms of the enzyme have been identified with each

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Asymmetrical dimethylarginine: A novel risk factor for coronary artery disease

Cited by 74 publications

References 38 publications

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

Redox Control of Protein Arginine Methyltransferase 1 (PRMT1) Activity

Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function

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