The effect of homocysteine on fibrinolytic system in human umbilical vein endothelial cells
Zhou, L-jun.; Mei, Y-fang.; Jin, H.; Wang, L-feng.; Gao, Q-ping.; Li, S-jun.; Li, W-min.
Zhonghua Xin Xue Guan Bing Za Zhi 33(9): 810-814
2005
ISSN/ISBN: 0253-3758 PMID: 16266457 Document Number: 593497
Objectives To investigate the relationship between homocysteine ( Hey) 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 mu mol/l, Hey with or without 15 mu mol/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 Hey was measured by reverse-phase high-performance liquid chromatography with recolumn 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 Hey at the concentration of 500 mu mol/L, compared with the control group (P<0.05). (2) The tPA mRNA and antigen levels were decreased significantly at concentration of 500 mu mol/l, of Hey, compared with that of 10 mu mol/l, Hcy (P<0.05), but compared with the control group(0 mu mol/L), the tPA mRNA and antigen levels of 10 mu mol/l, of Hey 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 mu mol/L Hey, compared with only Hey group (P<0.05). (4) Hey, tPA, and PAI-1 antigen levels were increased in AMI group. Hey is a independent risk factor of AMI (P<0.05). There weren't significant correlation between Hey and tPA or Hey 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.