Monocyte chemotactic protein 1 increases homing of mesenchymal stem cell to injured myocardium and neovascularization following myocardial infarction

Objective:To investigate the effect of MCP-1 on mesenchymal stem cells(MSCs) homing to injured myocardium in a rat myocardial infarction(MI) model.Methods:Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU.The Rats were divided into two groups. Monocyte chemotactic protein 1(MCP-I) expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1,2,4,7,14 and 28 days post operation in MCP-1 detection group.The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group.Then,a total of 5×10~6 cells in 2.5 ml of PBS were injected through the tail vein.The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection.Cardiac function and blood vessel density were assessed 28 days post injection.Results:Self-generating MCP-1 expression was increased at the first day,peaked at the 7day and decreased thereafter post MI and remained unchanged in sham operated hearts.The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group(P=0.000),the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups (P=0.000).Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups(P=0.000). Neovascularization in MCP-1 injected group significantly increased compared with that of other groups(P=0.000).Conclusion: Myocardial MCP-1 expression was increased only in the early phase post MI.MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.