The Role Of Monocyte Chemotactic Factor-1 In Isometric Contraction Exercise Promotes Ischemic Myocardial Collateral Artery Formation

Objective:to investigate the role of monocyte chemoattractant protein-1 in isometric exercise training induced arteriogenesis in rat model of mycardial ischemia.Method:Thirty-six male Sprague-Dawley rats were randomized into four groups:control group(CG),myocardial ischemia group(MI),exercise training group(ET),MCP-1 inhibitor group(LG).Rats were continuously administered 10 mg/kg subcutaneously isoproterenol for successive 2 weeks to establish the myocardial ischemia model in MI,ET and LG group..Isometric exercise training were performed in group ET and LG.The rats in group LG were given a gavage of MCP-1 inhibitor leflunomide.After 8 weeks of training,micro CT.relative collateral blood flow(RCBF),artery density(AD)and monocytes were used to measure arteriogenesis.Western blot analysis and real-time quantitative PCR were performed to assay protein and mRNA of MCP-1.Result:①The RCBF(0.285±0.012)of CG group was significantly lower than the rest three groups(P<0.001),The RCBF(0.436±0.012)of ET group was the highest(P<0.001),the RCBF(0.337±0.015)of LG group was higher than the CG group(P<0.001),but compared with that of MI group(0.346±0.016),there is no significant difference(P>0.05),②Artery density:The artery density(35.500±1.049)of ET group was significantly higher than the rest three groups(P<0.001),The artery density of MI group(25.000±1.414)was significantly higher than the CG group(21.667±1.751)(P=0.042),The artery density of LG group(23.833±2.927)had no significant difference compared with CG and MI group(compared with CG group:P=1;compared with MI group:P=0.39).③ The number of mononuclear cell:the number of mononuclear cell in ET group(144.085±10.869)was the highest of all groups(P<0.001),there was no significant difference of LG group(92.767 ± 18.426)compared with CG group(79.594± 12.740)and MI group(104.849 ±4.973)(compared with CG group:P=1;compared with MI group:P=1),the IOD of monocyte cell in MI group was higher than the CG group(P=0.020)。④The MCP-1 protein in myocardium:The MCP-1 expression in CG group(0.160±0.018)was lower than the MI group(0.241 ±0.025)(P=0.018)and the ET group(0.334±0.062)(P<0.001),there is no significant difference compared with LG group(0.184±0.019)(P=1);The MCP-1 expression in ET group was the highest(P<0.001),there is no difference between MI and LG group(P=0.208).⑤The MCP-1mRNA expression in myocardium:The MCP-1mRNA expression in CG group(1.737±0.306)was the lowest(compared with MI group:P=0.006;compared with ET group:P<0.001;compared with LG group:P=0.038),The MCP-lmRNA expression in ET group(5.717±0.656)was the highest(P<0.001),the MCP-ImRNA expression in MI group(2.890±0.471)and LG group(2.695±0.627)were no difference(P=1)。⑥The result of Micro CT:The number of collateral arterioles in ET group is higher compared with the rest three groups,.the number of collateral arterioles in MI group and LG group had no significant difference.⑦Correlation analysis:the MCP-1 expression was highly correlation with the IOD number of monocyte(r=0.8315,p<0.0001);the MCP-1 expression was highly correlation with the artery density(r=0.8629,p<0.0001);the MCP-1 expression was highly correlation with the RCBF(r=0.8798,p<0.0001).Conclusion:Isometric exercise training can increase MCP-1 in ischemic myocardium and promote the arteriogenesis.