title: [The effect of homocysteine on fibrinolytic system in human umbilical vein endothelial cells].
abstract: OBJECTIVE
  To investigate the relationship between homocysteine (Hcy) and the fibrinolytic system in acute myocardial infarction (AMI) and human umbilical vein endothelial cells (HUVEC).
  
  
  METHODS
  Cultured HUVEC was divided into 10 groups (0, 10, 50, 200, 500 micromol/L Hcy with or without 15 micromol/L of folic acid). There were 53 patients of acute myocardial infarction (AMI) and 48 healthy controls. The plasminogen activator inhibitor-1 (PAI-1) and activator of plasminogen (tPA) antigen levels in HUVEC's supernatant and plasma were measured with Elisa kit. Concentration of plasma Hcy was measured by reverse-phase high-performance liquid chromatography with precolumn derivatization and fluorometric detection in the patients and healthy controls. Total RNA was extracted using the guanidinium isothiocyanate method. The semi-quantification of PAI-1 and tPA mRNA in HUVEC was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  (1) PAI-1 mRNA and secreted protein levels were both significantly enhanced by Hcy at the concentration of 500 micromol/L, compared with the control group (P < 0.05). (2) The tPA mRNA and antigen levels were decreased significantly at concentration of 500 micromol/L of Hcy, compared with that of 10 micromol/L Hcy (P < 0.05), but compared with the control group (0 micromol/L), the tPA mRNA and antigen levels of 10 micromol/L of Hcy were much higher (P < 0.05). (3) The addition of folic acid reduced PAI-1 but increased tPA at both mRNA and protein levels, which were both obvious at concentrations of 500 micromol/L Hcy, compared with only Hcy group (P < 0.05). (4) Hcy, tPA, and PAI-1 antigen levels were increased in AMI group. Hcy is a independent risk factor of AMI (P < 0.05). There weren't significant correlation between Hcy and tPA or Hcy and PAI-1 in both groups (P > 0.05), although the coefficient correlation was higher in patients than in controls.
  
  
  CONCLUSIONS
  These results suggested that hyperhomo-cysteinemia increased the incidence of thrombotic disease, which may be caused by decreasing the activity of fibrinolytic system, whereas, folic acid may be protective against the toxic action of Hcy.
authors.affiliation: Cardiology Department, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. myfyxd@163.com
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Zhou
authors.forename: Yi-fang
authors.initials: YF
authors.lastname: Mei
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Lan-feng
authors.initials: LF
authors.lastname: Wang
authors.forename: Qian-ping
authors.initials: QP
authors.lastname: Gao
authors.forename: Shao-jun
authors.initials: SJ
authors.lastname: Li
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Li
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D010960:Plasminogen Activators