Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
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Coen van Guldener
Abstract
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is formed by methylation of arginine residues in proteins and released after proteolysis. In this reaction, S-adenosylmethionine is methyldonor and S-adenosylhomocysteine the demethylated product. ADMA and homocysteine are thus biochemically linked. Both plasma homocysteine and ADMA concentrations are increased in patients with renal dysfunction, probably as a result of an impairment in their metabolic, but not urinary, clearance. Hyperhomocysteinemia has been associated with an increased risk of cardiovascular disease in end-stage renal disease, especially in patients without malnutrition and inflammation. Also, plasma ADMA levels have been associated with cardiovascular disease in renal failure patients. Both homocysteine and ADMA are thought to mediate their adverse vascular effects by impairing endothelial, nitric oxide-dependent function resulting in decreased vasodilatation, increased smooth muscle cell proliferation, platelet dysfunction and increased monocyte adhesion. At the same time, it has been shown that the correlation between plasma ADMA and homocysteine is weak and that, in renal patients, the association of plasma ADMA carotid intima-media thickness, cardiovascular events and overall mortality is independent of homocysteine. This indicates that the negative vascular effects of ADMA and homocysteine have a different etiology. Treatment with folic acid substantially lowers homocysteine, but not ADMA concentration. So far, homocysteine-lowering therapy has not been very successful in decreasing cardiovascular disease. In patients with renal failure, ADMA reduction may be an interesting new goal in the prevention of cardiovascular disease.
Clin Chem Lab Med 2007;45:1683–7.
©2007 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Homocysteine research: alive and kicking!
- Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
- Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
- Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
- Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
- The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
- Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
- Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
- Hyperhomocysteinemia, DNA methylation and vascular disease
- Measuring subclinical atherosclerosis: is homocysteine relevant?
- Plasma protein homocysteinylation in uremia
- Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
- Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
- Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
- Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
- The molecular basis of homocysteine thiolactone-mediated vascular disease
- Importance of folate-homocysteine homeostasis during early embryonic development
- Association between homocysteine, vitamin B6 concentrations and inflammation
- Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
- Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
- Haptocorrin in humans
- Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
- Decreased p66Shc promoter methylation in patients with end-stage renal disease
- Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
- Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
- The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial
- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
Articles in the same Issue
- Homocysteine research: alive and kicking!
- Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
- Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
- Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
- Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
- The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
- Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
- Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
- Hyperhomocysteinemia, DNA methylation and vascular disease
- Measuring subclinical atherosclerosis: is homocysteine relevant?
- Plasma protein homocysteinylation in uremia
- Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
- Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
- Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
- Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
- The molecular basis of homocysteine thiolactone-mediated vascular disease
- Importance of folate-homocysteine homeostasis during early embryonic development
- Association between homocysteine, vitamin B6 concentrations and inflammation
- Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
- Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
- Haptocorrin in humans
- Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
- Decreased p66Shc promoter methylation in patients with end-stage renal disease
- Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
- Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
- The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial
- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
