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Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
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Dan Liao
Published/Copyright:
December 1, 2007
Abstract
Hyperhomocysteinemia (HHcy) is a significant and independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is unclear. We and others have reported that homocysteine (Hcy) is inversely correlated with plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apoA-I) in patients with coronary heart disease (CHD). We confirmed this negative correlation in mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine β-synthase (CBS). Severe HHcy (plasma Hcy 210 μmol/L) accelerates spontaneous arthrosclerosis in the CBS−/−/apoE−/− mice, reduces the concentration of circulating HDL, apoA-I, and large HDL particles, inhibits HDL function, and enhances HDL-C clearance. We have demonstrated further that Hcy (0.5–2 mmol/L) reduces apoA-I protein synthesis and secretion, but not RNA transcription in mouse primary hepatocytes. A different mechanism was proposed based on studies using the HepG2 cells showing that Hcy (5–10 mmol/L) inhibits apoA-I transcription via peroxisome proliferator-activated receptor-α (PPARα)-inhibition-dependent and -independent mechanisms. These studies suggest that Hcy-induced HDL-C and apoA-I inhibition represent a novel mechanism by which Hcy induces atherosclerotic CVD.
Clin Chem Lab Med 2007;45:1652–9.
Keywords: atherosclerotic cardiovascular disease; high-density lipoprotein metabolism; hyperhomocysteinemia
Received: 2007-9-4
Accepted: 2007-10-2
Published Online: 2007-12-01
Published in Print: 2007-12-01
©2007 by Walter de Gruyter Berlin New York
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- Hyperhomocysteinemia, DNA methylation and vascular disease
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- 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
Keywords for this article
atherosclerotic cardiovascular disease;
high-density lipoprotein metabolism;
hyperhomocysteinemia
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
