Interactions of Homocysteine, Nitric Oxide, Folate and Radicals in the Progressively Damaged Endothelium
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Olaf Stanger
Abstract
The endothelium exerts fundamental control over vascular tone, and injury to the endothelium followed by dysfunction is an early key event preceding manifestation of vessel pathology. Both elevated plasma homocysteine and low folate status have been identified as major and independent risk factors for atherosclerosis and have stirred an enormous and still increasing interest. The damaging effects of hyperhomocysteinemia on endothelial function are, at least in part, reversible through folate supplementation. Because of the inverse relationship between plasma folate and homocysteine levels, however, it is difficult to discriminate between their respective effects. Endothelial dysfunction refers mainly to reduced bioavailability of nitric oxide (NO), which is involved in homocysteinemediated vascular damage. Accumulating evidence further suggests that radical oxygen species are fundamentally involved in hyperhomocysteinemia. NO production is determined by cofactors such as tetrahydrobiopterin, which is oxidized and depleted in conditions of oxidant stress by peroxynitrite. Deficiency of tetrahydrofolate contributes to uncoupling, turning the NO synthase into a superoxide radical-producing enzyme. It appears that progression of vascular disease is likely to determine the multiple interactions between homocysteine, NO, oxygen radicals and folate. Folate has only recently been found to exert direct anti-oxidative effects and contribute to restoration of impaired NO metabolism. Understanding of the complex interactions between homocysteine, radicals, NO and folate offers promising perspectives in the individual treatment of vascular disease. Thus, preventive and therapeutic strategies may require a more distinct approach and better discrimination of target groups for greatest possible efficacy.
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
