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[Homocysteine as a nonlipid factor in the pathogenesis of atherosclerosis]
1Katedra i Klinika Nefrologii, Akademii Medycznej we Wrocławiu.
Insights
Elevated homocysteine levels, caused by genetic defects, are an independent risk factor for arteriosclerosis. Supplementation with folic acid and pyridoxine can reduce homocysteine and offer clinical benefits.
Area of Science:
- Biochemistry
- Genetics
- Vascular Biology
Context:
- Genetic abnormalities in homocysteine metabolism (transsulfuration, remethylation) lead to elevated plasma homocysteine.
- High homocysteine is linked to chronic renal failure and transplant patients.
- Homocysteine is an independent risk factor for arteriosclerosis in multiple circulatory systems.
Purpose:
- To investigate the role of homocysteine in arteriosclerosis.
- To explore the mechanisms by which homocysteine exerts its vascular effects.
- To evaluate the therapeutic potential of folic acid and pyridoxine in managing hyperhomocysteinemia.
Summary:
- Genetic defects in homocysteine degradation pathways result in hyperhomocysteinemia.
- Homocysteine directly damages endothelial cells, impairs protein C activation, enhances Lp(a) binding, induces tissue factor, and inhibits thrombomodulin.
- Folic acid and pyridoxine treatment effectively lowers homocysteine levels.
Impact:
- Homocysteine is a significant, independent risk factor for coronary, cerebral, and peripheral arteriosclerosis.
- Understanding homocysteine's vascular toxicity provides insights into arteriosclerosis pathogenesis.
- Folic acid and pyridoxine supplementation represent a viable clinical strategy to mitigate arteriosclerosis risk associated with hyperhomocysteinemia.
Abstract:
Genetic abnormalities in two metabolic steps in homocysteine degradation: transsulfuration and remetylation can cause raised plasma homocysteine concentration. Homocysteine appeared to be an independent arteriosclerotic risk factor in the coronary, cerebral and peripheral circulation and elevated homocysteine levels have been found in chronic renal failure patients undergoing hemodialysis treatment and in transplant patients as well. Homocysteine has a direct toxic effect on endothelial cells, reduces normal activation of protein C by endothelial cells, increases the binding of Lp(a) to plasmin-modified fibrin, induces tissue factor procoagulant activity and inhibits the cofactor activity of thrombomodulin. Treatment with folic acid and piridoxine can lower the high level of homocysteine and should be associated with a clinical benefit.