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The molecular basis of homocysteine thiolactone-mediated vascular disease

  • Hieronim Jakubowski
Veröffentlicht/Copyright: 8. Dezember 2007
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Band 45 Heft 12

Abstract

Accumulating evidence suggests that a metabolite of homocysteine (Hcy), the thioester Hcy-thiolactone, plays an important role in atherogenesis and thrombosis. Hcy-thiolactone levels are elevated in hyperhomocysteinemic humans and mice. The thioester chemistry of Hcy-thiolactone underlies its ability to form isopeptide bonds with protein lysine residues, which impairs or alters the protein's function. Protein targets for the modification by Hcy-thiolactone in human blood include fibrinogen, low-density lipoprotein, and high-density lipoprotein. Protein N-homocysteinylation leads to pathophysiological responses, including increased susceptibility to thrombogenesis caused by N-Hcy-fibrinogen, and an autoimmune response elicited by N-Hcy-proteins. Chronic activation of these responses in hyperhomocysteinemia over many years could lead to vascular disease. This article reviews recent evidence supporting the hypothesis that Hcy-thiolactone contributes to pathophysiological effects of Hcy on the vascular system.

Clin Chem Lab Med 2007;45:1704–16.

Keywords: atherosclerosis; autoantibodies; cystathionine β-synthase (CBS); dietary hyperhomocysteinemia; fibrinogen; genetic hyperhomocysteinemia; homocysteine thiolactone hypothesis; immune activation; methylenetetrahydrofolate reductase (MTHFR); protein N-homocysteinylation; thrombosis
Corresponding author: Hieronim Jakubowski, PhD, Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, 225 Warren Street, Newark, NJ 07101-1709, USA Phone: +1-973-972-4483, Fax: +1-973-972-8982,
Received: 2007-6-20
Accepted: 2007-8-29
Published Online: 2007-12-08
Published in Print: 2007-12-01

©2007 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. Homocysteine research: alive and kicking!
  2. Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
  3. Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
  4. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
  5. The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
  6. Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
  7. Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
  8. The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
  9. Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
  10. Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
  11. Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
  12. Hyperhomocysteinemia, DNA methylation and vascular disease
  13. Measuring subclinical atherosclerosis: is homocysteine relevant?
  14. Plasma protein homocysteinylation in uremia
  15. Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
  16. Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
  17. Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
  18. Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
  19. The molecular basis of homocysteine thiolactone-mediated vascular disease
  20. Importance of folate-homocysteine homeostasis during early embryonic development
  21. Association between homocysteine, vitamin B6 concentrations and inflammation
  22. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
  23. Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
  24. Haptocorrin in humans
  25. Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
  26. Decreased p66Shc promoter methylation in patients with end-stage renal disease
  27. Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
  28. Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
  29. 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
  30. Acknowledgement
  31. Contents, Volume 45, 2007
  32. Author Index
  33. Subject Index
https://doi.org/10.1515/CCLM.2007.338
Schlagwörter für diesen Artikel
atherosclerosis; autoantibodies; cystathionine β-synthase (CBS); dietary hyperhomocysteinemia; fibrinogen; genetic hyperhomocysteinemia; homocysteine thiolactone hypothesis; immune activation; methylenetetrahydrofolate reductase (MTHFR); protein N-homocysteinylation; thrombosis

Artikel in diesem Heft

  1. Homocysteine research: alive and kicking!
  2. Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
  3. Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
  4. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
  5. The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
  6. Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
  7. Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
  8. The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
  9. Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
  10. Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
  11. Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
  12. Hyperhomocysteinemia, DNA methylation and vascular disease
  13. Measuring subclinical atherosclerosis: is homocysteine relevant?
  14. Plasma protein homocysteinylation in uremia
  15. Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
  16. Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
  17. Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
  18. Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
  19. The molecular basis of homocysteine thiolactone-mediated vascular disease
  20. Importance of folate-homocysteine homeostasis during early embryonic development
  21. Association between homocysteine, vitamin B6 concentrations and inflammation
  22. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
  23. Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
  24. Haptocorrin in humans
  25. Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
  26. Decreased p66Shc promoter methylation in patients with end-stage renal disease
  27. Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
  28. Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
  29. 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
  30. Acknowledgement
  31. Contents, Volume 45, 2007
  32. Author Index
  33. Subject Index
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