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. |