Abstract:

BACKGROUND: Studies have shown that over-expression of heme oxygenase 1 (HO-1) has the effect of anti-inflammation. It is unclear whether injection of bone marrow mesenchymal stem cells (BMSCs) modified with heme oxygenase-1 (HO-1-BMSCs) in infarcted myocardium can significantly improve myocardial remodeling by regulating the ratio of matrix metalloproteinase (MMP) to tissue inhibitors of metalloproteinase (TIMP).
OBJECTIVE: To investigate the effects of transplantation of HO-1-BMSCs on regulating collagens and myocardial remodeling after myocardial infarction.
METHODS: BMSCs were cultured and amplificated with HO-1 adenovirus (Adv-HO-1) transfection in vitro. Myocardial infarction models in rats were established by ligating the left anterior descending coronary artery. One hour after modeling, HO-1-BMSCs and BMSCs were respectively transplanted into the infarcted myocardium of rats in a manner of multiple injections. The rats in the control group were given phosphate buffer in the same dose.
RESULTS AND CONCLUSION: Adv-HO-l stably expressed in BMSCs after transfection, while hHO-1-mRNA only expressed in HO-1-BMSCs. The expression of MMP2/9 in the HO-1-BMSCs group was decreased compared with that in the control group (P < 0.05), the reduction in Null- BMSCs was insignificant (P > 0.05). Compared with the control group, the expression of MMP2/3 was significantly increased in the other two groups, especially in the HO-1-BMSCs group (P < 0.05), but MMP1 did not change significantly (P > 0.05). The ratio of TIMP2 to MMP2 in cell transplantation groups was significantly increased, so was the ratio of TIMP3 to MMP9. Collagen was deposition decreased and ventricular was reduced in cell transplantation groups compared with the control group. The results showed that injection of HO-1-BMSCs can normalize the ratio of MMPs/TIMPs, as well as contribute to the revision of myocardial extracelluar remodeling.