| Background and Objective:Cardiovascular diseases have become the first killer of humanity,and the poor prognosis they cause brings a huge economic burden to society.For patients with coronary atherosclerotic heart disease,severe stenosis of coronary arteries can cause severe ischemia and hypoxia of the myocardium,eventually leading to the occurrence of cardiac remodeling and heart failure even sudden death.Good coronary collateral circulation(CCC)can significantly improve the prognosis of patients with coronary artery disease.However,there is a lack of serum markers to judge the level of coronary collateral circulation and clinical prognosis of patients with severe coronary artery stenosis in clinical practice.Angiopoietin-like protein 7(ANGPTL7)is associated with angiogenesis,and the pre-experiment of this study found that ANGPTL7 levels were associated with coronary collateral circulation in patients with coronary artery disease.Therefore,this study aimed to explore the association of ANGPTL7 with coronary collateral circulation and prognosis in patients with coronary artery disease,as well as to clarify the predictive ability of ANGPTL7 on coronary collateral circulation and clinical prognosis.Methods:1.Clinical study:72 patients who were hospitalized and underwent coronary angiography at Qilu Hospital of Shandong University from July 2021 to January 2022 were included.Patients with diameter stenosis ≥90%in at least one main coronary artery were divided into 2 groups according to Rentrop score:poor collateral circulation group(Rentrop score ≤1,n=23)and good collateral circulation group(Rentrop score>1,n=13);patients with diameter stenosis<90%in all main coronary arteries were the control group(n=36).General case information,laboratory results,ultrasonographic results,coronary angiography results,and usage of cardiovascular drug were collected from the study subjects in the hospital case system.Fasting venous blood was collected before coronary angiography,and ANGPTL7 concentration was measured by ELISA.The patients were followed up by telephone 1 year after discharge about whether and when MACE(Major adverse cardiovascular events)occurred.2.Experiments in vivo:C57BL/6J mice were divided into myocardial infarction group and sham-operated group as control.The left anterior descending coronary artery of mice in myocardial infarction group was ligatured to cause myocardial infarction.The sham-operated group was subjected to the same operation without ligation of the left coronary artery.After 4 weeks of modeling,left ventricular ejection fraction(LVEF)was measured,blood and heart was collected.Immunohistochemistry was used to determine the differences in collateral circulation between the two groups.Finally,ANGPTL7 concentrations of serum were measured in the myocardial infarction group(n=17)and control group(n=13)by enzyme-linked immunosorbent assay(ELISA).3.Experiments in vitro:Human umbilical vein endothelial cells were used.ANGPTL7 recombinant protein was added to the medium of the experimental group,at a final concentration of 1 μg/mL,and PBS was added to the medium of the control group.The effect of ANGPTL7 on the migratory ability of HUVEC was assessed by cell scratch test.The effect of ANGPTL7 on the proliferative ability of HUVEC was assessed by cellular immunofluorescence,Western blot,and CCK8 assays.The effect of ANGPTL7 on the tube formation ability of HUVEC was assessed by tube formation assay.4.Data analysis:All experimental data were statistically analyzed using the software SPSS 26.0.The results of all data analysis were considered statistically different at P<0.05.Results:1.Clinical Studies(1)Ventricular wall segmental motion abnormalities were significantly higher in the poor CCC group than in the control group,and NT-proBNP,hs-cTNI and ventricular wall segmental motion abnormalities were significantly higher in the good CCC group than in the control group(P<0.05).There were no statistically difference in the remaining baseline variables(P>0.05).(2)The rate of severe right coronary artery stenosis was significantly higher in the good CCC good group than in the poor CCC group(P<0.01),and there was no statistically significant difference in the remaining coronary angiographic results and the incidence of MACE between the two groups(P>0.05).(3)The ANGPTL7 concentrations in the control group,poor CCC group,and good CCC group were 1.30(0.69),1.08(0.94),and 2.11(1.31)ng/ml,and there were statistically differences in ANGPTL7 levels between the three groups(P<0.05).The ANGPTL7 concentrations in both the control group and poor CCC group were significantly lower than those in the good CCC group(P<0.05).Spearman correlation analysis showed a significantly positive correlation between ANGPTL7 and coronary collateral circulation grade(r=0.270,P<0.05).ROC curve analysis showed that the area under the curve of ANGPTL7 concentration predicting good coronary collateral circulation was 0.768(95%CI:0.630-0.905,P=0.003),and the optimal cut-off value was 2.01,with sensitivity of 61.5%and specificity of 84.7%.(4)36 patients with severe coronary stenosis were followed up for 13-52 weeks,and the total number of MACE cases was 11(30.6%),including 6(16.7%)cases of recurrent angina,3(8.3%)cases of coronary revascularization,1(2.8%)case of myocardial infarction,and 1(2.8%)case of cardiac death.There were no statistically significant difference between the good prognosis group and the poor prognosis group in clinical information,laboratory results,ultrasonographic results,coronary angiography results,treatment methods,and post-discharge medications except for septal thickness(P>0.05).(5)The ANGPTL7 concentrations in the good prognosis and poor prognosis groups were respectively 1.76(1.36)and 0.94(0.55)ng/ml,with statistical differences(P<0.01).Spearman correlation analysis showed a significantly negative correlation between ANGPTL7 and poor prognosis in patients with severe coronary stenosis(r=-0.444,P<0.01).Cox proportional risk regression model showed ANGPTL7 as an independent prognostic factor for the occurrence of MACE within 1 year(HR=0.268,95%CI:0.079-0.905,P=0.034).ROC curve analysis showed the area under the curve of ANGPTL7 concentration predicting no MACE within 12 months after discharge of 0.778(95%CI:0.590-0.966,P=0.003),and the optimal cut-off value was 0.98,with sensitivity of 92.0%and specificity of 63.6%.2.Experiments in vivo:The level of CD31 expression,also the level of collateral circulation of the myocardial infarction group was significantly higher than the control group(P<0.05),and LVEF of the myocardial infarction group 0.35(0.19)was significantly lower than the control group 0.59(0.15)(P<0.001).There was a statistical difference between myocardial infarction group(4.08±0.43ng/ml)with control group ANGPTL7(3.09±0.44ng/ml)in the ANGPTL7 concentration of mouse serum(P<0.001).3.Experiments in vitro:The ability of proliferation,migration and tube-forming of HUVEC were significantly increased after stimulation by ANGPTL7 with a statistical difference(P<0.05).Conclusion:1.ANGPTL7 concentrations were significantly positively correlated with good coronary collateral circulation.ANGPTL7 has strong specificity and sensitivity in predicting the level of coronary collateral circulation,and it can be used as a biomarker to evaluate the level of coronary collateral circulation.2.ANGPTL7 concentrations were significantly positively correlated with clinical prognosis in patients with severe coronary stenosis;the higher the serum ANGPTL7 levels,the better the clinical prognosis of patients.And it can be used as a biomarker to predict the clinical prognosis of patients with severe coronary stenosis. |
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