Pathogenesis Of Homocysteine ​​and Coronary Heart Disease Related To Its Inhibition Of The Fibrinolytic System

Background and objectives: Homocysteine(HCY) is a thiols-containing amino acid formed during the metabolism of methionine. The mild or moderate increase of the plasma HCY level may be an important risk factor for cardiovascular disease. The mechanism of the HCY-induced cardiovascular pathological changes is unclear now. Methylenetetrahydrofolate reductase(MTHFR) is involved in the remethylation pathway of HCY. A common missense mutation, which is a C-to-T substitution at nucletide position 677 of the MTHFR gene, is responsible for the elevated plasma HCY levels. Moreover, folate and vitamin B₁₂ (cobalamin) have regulatory effects on the plasma HCY level. At present, the studies in the field of HCY in China are few. The aim of our study was to investigate whether hyperhomocysteinemia was an independent risk factor associated with coronary artery disease (CAD) , to detect the association with MTHFR polymorphism and CAD, furthermore, to analysis the relationship betwwen HCY, folate and MTHFR gene. Endothelium damage leads to elevation of plasminogen activator inhibitor type l(PAI-l) and introcelluar calcium [Ca²⁺]i levels, which is closely associated with the thrombosis and atherosclerosis. It has been determined that high level of HCY can cause dysfunction of endothelial cell. According to this , we observed the effect of HCY on the PAI-1 activity and mRNA expression in vascular endothelial cells and on the [Ca²⁺]i in a single endothelial cell. It would be experimental basis for further investigating the mechanism of HCY-induced cardiovascular disease.Methods: In 161 patients with CAD as verified by coronary angiograms(CAD...