| Objective: The aim of this study was to investigate the correlation between the levels of circulating Angiotensin-converting enzyme 2(ACE2),Angiotensin(1-7)[Ang(1-7)],25 hydroxyvitamin D,25 hydroxylase,1α-hydroxylase,and 24 hydroxylase in children with orthostatic intolerance(OI).To explore the regulatory role of ACE2-Ang(1-7)-Mas axis and vitamin D(VD)in OI,so as to provide a potential endogenous biomarker and intervention target for the diagnosis and treatment of OI.Methods: In this study,we collected the whole blood samples of 95 children with syncope or syncope precursor symptoms who were diagnosed as OI and 307 healthy children who underwent outpatient physical examination in Lanzhou University Second Hospital from December 2019 to December 2020.Finally,84 OI patients and 84 healthy control children were included by gender and age 1:1 matching.According to the results of HUT/HUTT test,the subjects were divided into VVS group(51 cases)and POTS group(33 cases).There were 51 cases of VVS and 33 cases of POTS.The general data of all children were recorded,and 5 ml of fasting venous blood was collected from all children.The levels of 25(OH)D were detected by chemiluminescence method.The levels of ACE2,Ang(1-7),25 hydroxylase,1α-hydroxylase and 24 hydroxylase were detected by enzyme-linked immunosorbent assay(ELISA).SPSS25.0 was used for statistical analysis.Results:(1)The levels of serum ACE2,Ang(1-7),25(OH)D,24 hydroxylase and25 hydroxylase in OI group were significantly lower than those in control group(P<0.05),but there was no difference in 1α-hydroxylase level(P=0.92).(2)The levels of ACE2,Ang(1-7),25(OH)D,24 hydroxylase and 25 hydroxylase in OI group were lower than those in control group(P < 0.05)There was no difference in 1-α hydroxylase level(P>0.05).(3)There were no differences in ACE2,Ang(1-7),25(OH)D,1α-hydroxylase,24 hydroxylase and 25 hydroxylase levels between males and females in OI group(P>0.05).The 25(OH)D level of males in control group was higher than that of females in control group(P<0.05),but there was no difference in ACE2,Ang(1-7),1α-hydroxylase,24 hydroxylase and 25 hydroxylase levels between them(P>0.05).(4)The serum levels of ACE2,Ang(1-7),25(OH)D,24 hydroxylase and 25 hydroxylase in VVS group and POTS group were lower than those in control group(p<0.05),but there was no difference in 1α-hydroxylase level(P>0.05).There was no significant difference between VVS group and POTS group in ACE2,Ang(1-7).There was no significant difference in the levels of 25(OH)D,24 hydroxylase,25 hydroxylase and1α-hydroxylase between OI group and control group(P>0.05).(5)Serum Ang(1-7)was positively correlated with ACE2,25 hydroxylase and 24 hydroxylase in OI group,but negatively correlated with age and 1α-hydroxylase in OI group;ACE2 was positively correlated with 25 hydroxylase and 1α-hydroxylase in control group.In addition,in the control group,serum 25(OH)D was positively correlated with gender and negatively correlated with age.(6)Logistic regression analysis showed that the prevalence of OI increased by 10%(OR=0.900,95% CI;0.832-0.974),69.5%(OR=0.305,95% CI: 0.177-0.526)and 18.6%(OR=0.814,95% CI: 0.737-0.899)for every unit of decrease in the ratio of 25(OH)D,25 hydroxylase,Ang(1-7)to ACE2.(7)The sensitivity and specificity of Ang(1-7)were 81.0% and 76.2% with 31.85 ng/ m L as the cut-off value for OI,indicating good sensitivity.When the ratio of Ang(1-7)to ACE2 was 11.595 as the cut-off value,the sensitivity and specificity for OI diagnosis were 77.4% and 88.1%,which showed good specificity.When 25(OH)D,Ang(1-7),ACE2,Ang(1-7)/ACE2 and 25 hydroxylase were used as the combined factors,the sensitivity and specificity for OI diagnosis were 86.9% and 81.0% when the critical value of the combined factors was 38.54,indicating a strong predictive ability.Conclusion:(1)The decrease of serum Ang(1-7)/ ACE2 ratio,25(OH)D level and25 hydroxylase level is one of the important factors of OI,which may be also the main reason of renin aldosterone paradox in children with POTS;(2)The deficiency25(OH)D in OI children may participate in the occurrence of OI by regulating ACE2ang(1-7)-MAS axis;(3)Monitoring Ang(1-7)and ACE2 may be new biomarkers for OI diagnosis. |
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