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Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

Bottom Line: Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis.In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells.These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

ABSTRACT
l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review.

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Representation of the main properties and functions of normal endothelium.
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f3-ijms-13-11288: Representation of the main properties and functions of normal endothelium.

Mentions: Several studies have found that the plasma levels of ADMA in healthy subjects with no apparent cardiovascular disease are related to age, blood pressure, insulin resistance, and carotid intima-media thickness [30,31]. These findings suggest that an increase in ADMA levels is a marker for arteriosclerotic changes. For this reason, ADMA levels have been used for assessing cardiovascular risk [32,33]. Further, it is known that ADMA is mainly absorbed by endothelial cells, extracellular levels being 5 to 10 times lower. This means that slight changes in plasma levels of ADMA are sufficient to significantly change intracellular ADMA levels and, thereby, modify NO production and contribute to the development of cardiovascular disease. Under pathological conditions, there may be a 3- to 9-fold increase in plasma levels of ADMA, and this would inhibit NO production by 30% to 70% [34]. This explains why this metabolite can be used as a cardiovascular marker, as a decrease in NO production by the some of the endothelium leads to adverse vascular effects (Figure 3) such as dysregulation of blood pressure, prevention of vasodilation, loss of antithrombotic activity, problems in homeostasis and fibrinolysis, and inhibition of platelet aggregation, among others [35,36]. Given this, the effect of ADMA on the Arg-NO pathway is of particular importance in conditions associated with vascular wall damage, such as hypercholesterolaemia, high blood pressure, smoking, diabetes and obesity.


Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

Representation of the main properties and functions of normal endothelium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472745&req=5

f3-ijms-13-11288: Representation of the main properties and functions of normal endothelium.
Mentions: Several studies have found that the plasma levels of ADMA in healthy subjects with no apparent cardiovascular disease are related to age, blood pressure, insulin resistance, and carotid intima-media thickness [30,31]. These findings suggest that an increase in ADMA levels is a marker for arteriosclerotic changes. For this reason, ADMA levels have been used for assessing cardiovascular risk [32,33]. Further, it is known that ADMA is mainly absorbed by endothelial cells, extracellular levels being 5 to 10 times lower. This means that slight changes in plasma levels of ADMA are sufficient to significantly change intracellular ADMA levels and, thereby, modify NO production and contribute to the development of cardiovascular disease. Under pathological conditions, there may be a 3- to 9-fold increase in plasma levels of ADMA, and this would inhibit NO production by 30% to 70% [34]. This explains why this metabolite can be used as a cardiovascular marker, as a decrease in NO production by the some of the endothelium leads to adverse vascular effects (Figure 3) such as dysregulation of blood pressure, prevention of vasodilation, loss of antithrombotic activity, problems in homeostasis and fibrinolysis, and inhibition of platelet aggregation, among others [35,36]. Given this, the effect of ADMA on the Arg-NO pathway is of particular importance in conditions associated with vascular wall damage, such as hypercholesterolaemia, high blood pressure, smoking, diabetes and obesity.

Bottom Line: Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis.In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells.These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

ABSTRACT
l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review.

Show MeSH
Related in: MedlinePlus