Effect of resistin on MMP-9 in human coronary artery endothelial cells

Abstract:

Objective：To investigate the expression of matrixmetalloproteinases-9（MMP-9） in human coronary artery endothelial cells （HCAECs） and to explore its underlying mechanism. Methods：HCAECs were incubated by 1% fetal bovine serum（FBS） in DMEM/F12 culture medium in six different group：（1）blank control（Con）group：without resistin；（2）Res20 group：with 20 ng/ml resistin；（3）Res40 group：with 40 ng/ml resistin；（4）Res100 group：with 100 ng/ml resistin；（5）Res40+U0126 group：incubating HCAECs with ERK inhibitor U0126 （20 mmol/L） pretreatment for 1 h ，then adding 40 ng/ml resistin；（6）U0126 group：with ERK inhibitor U0126 （20 mmol/L）. After 24 h，MMP-9 and tissue inhibitor of metalloproteinase-1（TIMP-1） mRNA and protein levels were measured by RT-PCR and ELISA. HCAECs p-ERK1/2 and ERK1/2 protein levels were measured by Western blot. Results：Compared with those in Con group，MMP-9 mRNA and protein levels were increased in Res20，Res40，Res100 groups（P＜0.05） and TIMP-1 mRNA and protein levels were decreased（P＜0.05）. MMP-9 mRNA and protein levels in Res 40+U0126 group were lower than those in Res40 group（P＜0.05） while there is no obvious change of TIMP-1 mRNA and protein levels. Compared with those in Con group，U0126 and Res40+U0126 group，p-ERK1/2 protein levels were higher in Res40 group（P＜0.05）. Conclusions：Expression of resistin can down-regulate the TIMP-1 and induce MMP-9 synthesis. The ERK1/2 is involved in MMP-9 expression in HCAECs exposed to re－sistin. These results suggest an active role of resistin in the pa－thophysiology of resistin-induced cardiovascular disease.