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Hyperhomocysteinemia, DNA methylation and vascular disease
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Md S. Jamaluddin
Published/Copyright:
December 8, 2007
Abstract
Hyperhomocysteinemia (HHcy) has been established as a potent independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is largely unknown. We were the first to propose that hypomethylation is the key biochemical mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We reported that clinically relevant concentrations of Hcy (10–50 μmol/L) exerts highly selective inhibitory effects on cyclin A transcription and EC growth through a hypomethylation related mechanism, which blocks cell cycle progression and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading to cyclin A chromatin remodeling. We found that adenovirus-transduced DNMT1 gene expression reverses the inhibitory effect of Hcy on cyclin A expression and EC growth inhibition. We hypothesize that DNA hypomethylation is a key biochemical mechanism responsible for Hcy-induced cyclin A suppression and growth inhibition in EC and contributes to CVD.
Clin Chem Lab Med 2007;45:1660–6.
Keywords: atherosclerosis; cardiovascular disease; chromatin remodeling; DNA methylation; endothelial cell growth; homocysteine
Received: 2007-8-6
Accepted: 2007-10-2
Published Online: 2007-12-08
Published in Print: 2007-12-01
©2007 by Walter de Gruyter Berlin New York
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- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
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- 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
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- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
Keywords for this article
atherosclerosis;
cardiovascular disease;
chromatin remodeling;
DNA methylation;
endothelial cell growth;
homocysteine
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
