Effects of low-molecular weight heparin on MMP-2, TIMP-2 expression and invasiveness of cytotrophoblastic cells

AIM: To investigate the hypothesis that low-molecular weight heparin (LMWH) regulates in vitro cytotrophoblast invasiveness and production of metalloproteinases-2 (MMP-2), tissue inhibitor of metalloproteinas-2 (TIMP-2). METHODS: Chorionic villi tissue of normal 6-8 weeks pregnancy was obtained. Trophoblastic cells were collected by trypsin-collagenase digestion and Percoll gradient centrifugation. The cytotrophoblastic cells were cultured for 24 h and divided into 4 groups according to the concentrations (1.0×102 IU/L, 1.0×103 IU/L or 1.0×104 IU/L) of LMWH adding into the medium. The contents of MMP-2 and TIMP-2 in cell culture supernatants were measured by the method of ELISA. Cytotrophoblast invasiveness was determined by Transwell chamber assay. RESULTS: With the increasing concentrations of LMWH, the invasion activity of cytotrophoblastic cells and MMP-2 secretion were increased. At concentration of 1.0×103IU/L, LMWH greatly enhanced cytotrophoblast invasiveness and the expression of MMP-2 (P<0.05). The levels of TIMP-2 were decreased after intervention with LMWH. At concentration of 1.0×103IU/L or 1.0×104 IU/L, LMWH induced a significant decrease in TIMP-2 expression. No significant difference between group 1×103IU/L and group 1.0×104 IU/L was observed (P>0.05). CONCLUSION: LMWH might regulate cytotrophoblast invasiveness in vitro by influencing the expression of MMP-2 and TIMP-2 in cytotrophoblastic cells.