Association Of MicroRNA-210 With EphrinA3 And VEGF In Plasma Of Patients With Coronary Heart Disease And Its Effect On The Formation Of Collateral Circulation

Objective: The aim of our study is to investigate the association of micro RNA-210 with Ephrin A3 and VEGF in plasma of patients with coronary heart disease and its effect on the formation of coronary collateral circulation(CCC)。Method: This study enrolled a total of 255 coronary heart disease patients with ≥90% stenosis in at least one epicardial coronary artery.Coronary stenosis was assessed by Gensini scores.Coronary stenosis was assessed by Gensini scores.According to the Rentrop grading,patients were divided into a good CCC group(Rentrop ≥ 2)(n=107)and a poor CCC group(Rentrop<2)(n=148).In addition,79 patients were selected from the patients with no coronary artery stenosis as normal control.Real-time PCR was used to measure the expression of mi R-210 in plasma.The concentration of VEGF and Ephrin A3 was measured by ELISA.After the hypoxia exposure of human coronary artery endothelial cells(HCAECs),we measured the expressions of mi R-210 and Ephrin A3 m RNA in HCAECs by q PCR.The expression of Ephrin A3 protein in HCAECs was detected by Western blot.SPSS 22.0 was applied to analyze the data.Results: 1.Compared with that in poor CCC group,the Gensini score in good CCC group was significantly higher(109.79±37.30 vs 64.26±36.59,p<0.05),and the HDL-C was significantly lower in good CCC group(1.04±0.20 mmol/L vs 1.16±0.26 mmol/L,p<0.05).2.Compared with control group,the expression level of mi R-210(2.31±0.15 vs 1.39±0.13,p<0.01)was significantly upregulated in plasma of patients with coronary heart disease,and the concentration of Ephrin A3(564.40±8.53 pg/m L vs 618.70±19.64 pg/m L,p<0.05)was significantly lower,and the concentration of VEGF was significantly higher(2990.00 ±50.55 pg/m L vs 2766.00±80.94 pg/m L,p<0.05).3.Compared with poor CCC group,the expression level of mi R-210 in plasma of patients with coronary heart disease was significantly upregulated(3.07±0.27 vs 1.77±0.14,p<0.01).And the expression level of mi R-210 in plasma of patients was also significantly upregulated than that in control group(3.07±0.27 vs 1.39±0.13,p<0.01).The expression level of mi R-210 was upregulated in patients with poor CCC compared with that in control group(1.77±0.14 vs 1.39±0.13,p= 0.114),but the difference was not statistically significant.The concentration of Ephrin A3 in plasma of patients was significantly lower in good CCC group compared with that in poor CCC group(530.90±14.04 pg/m L vs 588.20±10.22 pg/m L,p<0.01),and was also significantly lower than that in control group(530.90±14.04 pg/m L vs 618.70±19.64 pg/m L,p<0.01).Ephrin A3 was also significantly lower in poor CCC group compared with that in the control group(588.20±10.22 pg/m L vs 618.70±19.64 pg/m L,p<0.01).The concentration of VEGF in plasma of patients was significantly higher in good CCC group in comparison with poor CCC group(3157.00±86.55 pg/m L vs 2872.00±59.08 pg/m L,p<0.05),and was also significantly higher than that in control group(3157.00±86.55 pg/m L vs 2766.00±80.94 pg/m L,p<0.01).At the same time,the concentration of VEGF was higher in patients with poor CCC compared with that in control group(2872.00±59.08 pg/m L vs 2766.00±80.94 pg/m L,p<0.01).4.Pearman correlation analysis showed that during the formation of CCC there was a low positive correlation between the expression level of mi R-210 and the concentration of VEGF in plasma of patients with coronary heart disease(r= 0.2544,p<0.001).And the concentration of Ephrin A3 showed a low negative correlation with VEGF(r=-0.1741,p<0.05),when mi R-210 was negatively correlated with Ephrin A3(r=-0.3967,p <0.001).At the same time the expression level of mi R-210 in patients with coronary heart disease was positively correlated with Gensini scores(r=0.3007,p<0.001),and the concentration of VEGF was positively correlated with Gensini scores(r=0.1218,p<0.05).The concentration of HDL-C was negatively correlated with the Gensini score(r=-0.2553,p < 0.001).There was no correlation between HDL-C and VEGF(r=-0.0016,p>0.05)according to the Pearman correlation analysis.5.The expression level of mi R-210 and Ephrin A3 m RNA in HCAECs cells was upregulated with the lack of oxygen,and the expression level of Ephrin A3 protein was downregulated with the lack of oxygen.Conclusions: 1.The expression level of mi R-210 in plasma of patients with coronary heart disease promotes the formation of coronary collateral circulation,which is positively correlated with VEGF,and negatively correlated with Ephrin A3.2.The expression level of mi R-210 is positively correlated with coronary artery stenosis and hypoxia.