Effects of high glucose on MMP-2 and TIMP-2 expressions and proliferation of vascular smooth muscle cells

Objective To investigate the effect of high glucose on expressions of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2) as well as on the proliferation of vascular smooth muscle cells(VSMCs).Methods After being cultured and passaged,the VSMCs were divided into four groups and cultured in four different culture conditions for 72 hours,respectively:normal glucose group(NG group,5.5 mmol/L Glu),mannitol group(5.5 mmol/L Glu + 19.5 mmol/L mannitol),high glucose group(HG group,25 mmol/L Glu) and GM6001 group(25 mmol/L Glu + 5 μmol/L GM6001).Then,the expressions of MMP-2 and TIMP-2 were detected by RT-PCR technique,and the proliferation of VSMCs was evaluated by MTT method in four culture conditions.Results The expressions of MMP-2 and TIMP-2 mRNA were significantly higher in HG group than in NG group(P0.01).Compared with that in NG group,the ratio of relative expression of MMP-2 and TIMP-2 mRNA in HG group was also significantly increased(P0.01).However,mannitol or GM6001 group did not differ significantly from NG group in the expressions or the ratio of relative expression of MMP-2 and TIMP-2 mRNA(P0.05).The proliferation of VSMCs increased significantly at different time points in HG group as compared with NG group(P0.05),but mannitol or GM6001 group did not significantly differ from NG group respectively(P0.05).Conclusion High glucose promotes proliferation of VSMCs,which may be mediated through the imbalance of MMP-2 and TIMP-2 expressions.