Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction
-
Norbert Weiss
Abstract
Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteine-induced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Where Are We Standing in Homocysteine Research?
- DACH-LIGA Homocystein (German, Austrian and Swiss Homocysteine Society): Consensus Paper on the Rational Clinical Use of Homocysteine, Folic Acid and B-Vitamins in Cardiovascular and Thrombotic Diseases: Guidelines and Recommendations
- Hyperhomocysteinaemia as a Risk Factor for Venous Thrombosis: An Update of the Current Evidence
- Does Homocysteine Cause Hypertension?
- Homocysteine Metabolism in Renal Disease
- Hyperhomocysteinemia and B-Vitamin Deficiencies in Infants and Children
- The Role of Genetic Factors in the Development of Hyperhomocysteinemia
- New Basis of the Neurotrophic Action of Vitamin B12
- Hyperhomocysteinemia and Immune Activation
- Interactions of Homocysteine, Nitric Oxide, Folate and Radicals in the Progressively Damaged Endothelium
- Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction
- Homocysteine-Thiolactone and S-Nitroso-Homocysteine Mediate Incorporation of Homocysteine into Protein in Humans
- Association of Asymmetric Dimethylarginine and Endothelial Dysfunction
- Genetic Determinants of Folate and Vitamin B12 Metabolism: A Common Pathway in Neural Tube Defect and Down Syndrome?
- Functional Vitamin B12 Deficiency and Determination of Holotranscobalamin in Populations at Risk
- Holotranscobalamin as a Predictor of Vitamin B12 Status
- Hyperhomocysteinemia and B-Vitamin Status after Discontinuation of Oral Anticoagulation Therapy in Patients with a History of Venous Thromboembolism
- Measurement of Carotid Plaque and Effect of Vitamin Therapy for Total Homocysteine
- Folate Improves Endothelial Function in Patients with Coronary Heart Disease
- The Impact of Hyperhomocysteinemia as a Cardiovascular Risk Factor in the Prediction of Coronary Heart Disease
- Homocysteine Increases during Endurance Exercise
- Comparison of the Influence of Volume-Oriented Training and High-Intensity Interval Training on Serum Homocysteine and Its Cofactors in Young, Healthy Swimmers
- Analysis of the Transcobalamin II 776C>G (259P>R) Single Nucleotide Polymorphism by Denaturing HPLC in Healthy Elderly: Associations with Cobalamin, Homocysteine and Holo-Transcobalamin II
- Meetings and Awards
Articles in the same Issue
- Where Are We Standing in Homocysteine Research?
- DACH-LIGA Homocystein (German, Austrian and Swiss Homocysteine Society): Consensus Paper on the Rational Clinical Use of Homocysteine, Folic Acid and B-Vitamins in Cardiovascular and Thrombotic Diseases: Guidelines and Recommendations
- Hyperhomocysteinaemia as a Risk Factor for Venous Thrombosis: An Update of the Current Evidence
- Does Homocysteine Cause Hypertension?
- Homocysteine Metabolism in Renal Disease
- Hyperhomocysteinemia and B-Vitamin Deficiencies in Infants and Children
- The Role of Genetic Factors in the Development of Hyperhomocysteinemia
- New Basis of the Neurotrophic Action of Vitamin B12
- Hyperhomocysteinemia and Immune Activation
- Interactions of Homocysteine, Nitric Oxide, Folate and Radicals in the Progressively Damaged Endothelium
- Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction
- Homocysteine-Thiolactone and S-Nitroso-Homocysteine Mediate Incorporation of Homocysteine into Protein in Humans
- Association of Asymmetric Dimethylarginine and Endothelial Dysfunction
- Genetic Determinants of Folate and Vitamin B12 Metabolism: A Common Pathway in Neural Tube Defect and Down Syndrome?
- Functional Vitamin B12 Deficiency and Determination of Holotranscobalamin in Populations at Risk
- Holotranscobalamin as a Predictor of Vitamin B12 Status
- Hyperhomocysteinemia and B-Vitamin Status after Discontinuation of Oral Anticoagulation Therapy in Patients with a History of Venous Thromboembolism
- Measurement of Carotid Plaque and Effect of Vitamin Therapy for Total Homocysteine
- Folate Improves Endothelial Function in Patients with Coronary Heart Disease
- The Impact of Hyperhomocysteinemia as a Cardiovascular Risk Factor in the Prediction of Coronary Heart Disease
- Homocysteine Increases during Endurance Exercise
- Comparison of the Influence of Volume-Oriented Training and High-Intensity Interval Training on Serum Homocysteine and Its Cofactors in Young, Healthy Swimmers
- Analysis of the Transcobalamin II 776C>G (259P>R) Single Nucleotide Polymorphism by Denaturing HPLC in Healthy Elderly: Associations with Cobalamin, Homocysteine and Holo-Transcobalamin II
- Meetings and Awards
