Role of granulocyte-macrophage colony-stimulating factor in promoting angiogenesis of rat with acute myocardial injury

Objective To study the effect of granulocyte-macrophage colony-stimulating factor(GM-CSF)on angiogenesis of rat with acute myocardial injury induced by isoproterenol(Iso). Methods A total of 60 adult male Wistar rats were randomly divided into 3 groups: normal control group, GM-CSF pretreatment group (GM-CSF group), and lso injury group, 20 rats in each group. GM-CSF group was administered recombinant human(rh)GM-CSF(5.0 μg/kg), through tail intravenous injection once a day for three days. Then the GM-CSF group and the Iso injury group were anesthetized by intraperitoneal injection of lso( 15.0 mg/kg) once a day for three days. The same dose of saline was administered in the same way to the control rats. Ten days after injection, pathological changes of myocardial damage and infarct area were examined by immunohistochemistry. The mRNA expression levels of polypeptide antigen (CD34), vascular endothelial growth factor (VEGF) and its receptor KDR/flk- 1 were measured by RT-PCR. Results The difference of myocardial necrosis area between groups was statistically significant(F=10.07, P < 0.01), in which GM-CSF group[(37.37 ± 12.98)%] was significantly less than Iso injury group[(45.51 ±14.96)%, P < 0.05]. The difference of myocardial neovascularization density index of rats between groups was statistically significant ( F = 25.54, P < 0.05 ), in which GM-CSF group [(3980.05 ± 477.22) No/mm2] was significantly higher than Iso injury group((2605.93±361.49)No/mm2,P<0.01).The differences of myocardial CD34,VEGF,KDR/flk-1 mRNA expression between groups were statistically significant(F=17.83,4.29,4.10,all P<0.01).Compared to Iso mjury group[CD34(23.85±6.06),VEGF(31.80±8.05),KDR/flk-1(30.16±8.01)]were higher in the GM-CSF group[CD34(44.04±10.13),VEGF(49A±11.59),and KDR/flk-1(46A9±7.90),all P<0.01].The expressions of myocardiM VEGF mRNA and its receptor KDR/flk-1 mRNA was positively correlated(r=0.725,R2=0.526,P<0.01).Conclusions GM-CSF prelreatmcnt increases the density ofnew blood vessels in myocardium,and reduces the Iso-induced myocardial injury in rats. Key words: Myocardial infarction; Granulocyte-macrophage colony-stimulating factor; Isoprenaline; Vasculogenesis