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DAMAGING EFFECTS OF HOMOCYSTEINE |
| 1. Endothelial cell dysfunction. Decreased eNO bioavailability. |
| 2. Endothelial cell toxicity – apoptosis. |
| 3. Smooth muscle cell proliferation – myointimal hyperplasia and hypertrophy. Hcy induces Ca++ second messenger in vascular SMCs. |
| 4. Extracellular matrix remodeling – activation of redox sensitive MMPs. Decreased bioavailability of eNO. Resulting in ECM fibrosis. |
| 5. Promotes vasoconstriction |
| 6. Promotes LDL-cholesterol modification: LDL-C – Homocysteine thiolactone aggregates. |
| 7. Pro-inflammatory: MCP-1 and IL-8. |
| 8. Promotes macrophage – foam cell formation via LDL-cholesterol modification. |
| 9. Prothrombotic: Hcy reduces thrombomodulin and heparan sulfate levels. Decreases protein C activity and inhibits binding of tPA to endothelial cells. Hcy activates factors V and XII and increases tissue factor expression. Hcy induces platelet adhesiveness and aggregation. |
| 10. Pro oxidative and redox stress via reactive oxygen species formation. |
| 11. Induces 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in endothelial cells. |
| 12. Promotes oxidation of BH4 to BH2 and BH3, which uncouples the eNOS reaction resulting in superoxide formation and a decrease in eNO. |
| 13. Promotes atherogenesis, arteriosclerosis, atherosclerosis, and atheroscleropathy. |
Hayden and Tyagi Nutrition Journal 2004 3:4 doi:10.1186/1475-2891-3-4 |