The Significance Of AECA In The Progression Of COPD And Its Relationship With VEGF And MiRNA-23a

Objective:In this study,the levels of anti-endothelial cell antibody(AECA),vascular endothelial growth factor(VEGF),and microRNA-23a(miRNA-23a)in plasma of patients with chronic obstructive pulmonary disease(COPD)and normal population were detected.Then,the stable COPD patients were dynamically followed up to explore the significance of AECA in COPD sustained progression and its relationship with VEGF and miRNA-23a,which provides a theoretical basis for the clinical study of the pathogenesis of the continuous progression of the disease.Methods:Part of COPD patients and healthy subjects who were hospitalized or treated in Guizhou Provincial People’s Hospital from October 2019 to February 2020 were selected.The subjects were divided into three groups: stable COPD group(93 cases),acute exacerbation group(36 cases),and healthy control group(30 cases).The stable COPD group was further divided into a pair of subgroups: the higher AECA group and the lower AECA group based on the median of AECA(386.17pg/mL)in the stable group(>386.17pg/mL belonged to the higher group,and <386.17pg/mL was included in the lower group).Therefore,according to the grouping standard,the sample datum in the middle(AECA=386.17pg/mL)was omitted,and the sample size of the higher group and the lower group of AECA accounted for 46 cases respectively).1.VEGF and AECA levels in peripheral blood of the three groups were detected by ELISA,and miRNA-23a levels in peripheral blood were detected by q RT-PCR.At the same time,pulmonary function test was performed in stable COPD stage patients with pulmonary function instrument,and the frequency of acute exacerbations in stable COPD stage patients in the previous 1 year was counted and mMRC score was performed.2.The higher and lower AECA groups were followed up at intervals of 6 and 12 months.Follow-up test indexes included AECA、VEGF、miRNA-23a,and further lung function tests were performed(FEV1、FEV1/FVC、FEV1%pred),the frequency of acute exacerbations in the previous 1 year and dyspnea score(mMRC score)in stable COPD stage counted.Results:1.Comparison of AECA,VEGF and miRNA-23a in acute exacerbation of COPD,stable COPD group and normal control group(1)Comparison of AECA and VEGF levels among the three groups: they were higher in the acute exacerbation stage of COPD group than in the stable group and healthy control group,and the levels in stable COPD group were higher than those in healthy control group,with statistical significance(P<0.05).(2)Comparison of miRNA-23a levels among the three groups: miRNA-23a levels were higher in the stable COPD group than in the acute exacerbation group and the healthy control group,and they were higher in the acute exacerbation group than in the healthy control group,with statistical significance(P<0.05).2.Comparison of related indexes between subgroups in stable COPD group The miRNA-23a levels in the higher AECA group were lower than those in the lower AECA group,and the difference was statistically significant(P<0.05),which was not comparable.Therefore,the corresponding dynamic follow-up comparison of miRNA-23a levels between the two subgroups was not performed in the later period.3.Overall comparison of related indicators before and after follow-up in stable COPD group(1)The levels of AECA and VEGF in patients followed up for 6 months and 12 months were higher than the baseline level before follow-up,and the levels after 12 months were higher than those after 6 months.The miRNA-23a levels after 12 months were lower than those before the follow-up,and the difference was statistically significant(P<0.05).(2)FEV1,FEV1/FVC and FEV1%pred were all lower than the baseline in the follow-up after 12 months(the latter two indexes were also lower than those after 6 months),with statistically significant differences(P<0.05).(3)The number of acute exacerbations and mMRC score after 6 months of follow-up were lower than before,while after 12 months of follow-up,they were higher than those after 6 months,with statistical significance(P <0.05).4.Comparison of relevant indexes before and after follow-up between the higher and lower AECA groups(1)The levels of AECA and VEGF in both high and low AECA groups after 6and 12 months follow-up were higher than those before follow-up,and the levels after12 months of follow-up were higher than those after 6 months.After 12 months of follow-up,they were still higher in the higher AECA group than in the lower AECA group during the same period,and the differences were statistically significant(P<0.05).(2)After 12 months of follow-up,FEV1,FEV1%pred and FEV1/FVC in the high AECA group were lower than those before and after 6 months of follow-up(the first two indicators after 6 months of follow-up were also lower than those before follow-up).The FEV1%pred in the lower AECA group after 12 months of follow-up was lower than that before and after 6 months of follow-up.After 12 months of follow-up,FEV1,FEV1%pred and FEV1/FVC in the higher AECA group were lower than those in the lower AECA group during the same period(the first two indicators in the higher AECA group after 6 months of follow-up were still lower than those in the lower AECA group during the same period),with statistically significant differences(P <0.05).(3)The frequency of acute exacerbation and mMRC score in the higher AECA and lower AECA groups after 6 months were lower than those before follow-up,but after 12 months,they were higher than after 6 months.The number of previous acute exacerbations and mMRC score in the higher AECA group were higher than those in the lower AECA group during the same period after 6 months and 12 months of follow-up,with statistical significance(P<0.05).5.Spearman correlation analysis: the AECA was positively correlated with VEGF(rs=0.239,P=0.006)and negatively correlated with miRNA-23a(rs=-0.367,P<0.001)in COPD patients.Conclusions:1.Abnormal expression of AECA,VEGF and miRNA-23a may be involved in the occurrence of COPD,and AECA may promote the progression of COPD;2.In the continuous progression of COPD,the expression of AECA may continuously promote the expression of VEGF;3.AECA expression was negatively correlated with miRNA-23a expression in COPD patients.