Correlation Of UPS And SST2 In Myocardial Remodeling In Patients With Heart Failure

Background and Objectives:Myocardial remodeling(MR)is one of the important mechanisms for the occurrence and development of heart failure(HF).Cardiomyocyte apoptosis,myocardial fibrosis and abnormal protein accumulation occurred early in HE.Ubiquitin Protease system(UPS)is the main pathway for abnormal protein degradation in cells,which is related to myocardial remodeling.At present,there are few reports on serum changes of UPS in HF patients.Soluble growth stimulation exPressed gene 2(sST2)is a new serum marker.A large number of literatures show that sST2 can reflect the degree of myocardial fibrosis and ventricular remodeling,and the change of sST2serum level is closelyrelated tothe prognosis of patients with HF.Many studies have shown that the increase of ubiquitinated proteins leads to the degradation of ST2.UPS is related to IL-33/ST2,and UPS is one of the factors regulating IL-33/ST2.Since UPS and sST2 are the related factors of HF,our previous study found that the use of proteasome inhibitor MG-132 in the HF model after myocardial infarction in rats could affect the serum sST2 in rats.Therefore,this study intends to observe the changes in the levels of key enzyme ubiquitin(Ub),26S proteasome and sST2 in serum UPS of HF patients,and to explore whether there is a correlation between UPS and sST2.Methods:Thirty-seven serum samples of HF patients(18 males and 19 females,aged 35-90 years old,with an average of(65.73±11.9)years old)from August 2020 to December 2020 in Department of Cardiovascular Medicine,First Affiliated Hospital of Dali University were selected.All patients with heart failure met the diagnostic criteria of《Chinese Guidelines for Diagnosis and Treatment of Heart Failure 2018》".Healthy control group 37 cases,male 19 cases,female 18 cases,age 42～86 years old,average(63.62±10.5)years old,were the same period in our hospital physical examination center to exclude related factors of healthy people.Patients with heart failure in the morning of admission fasting venous blood5ml,3000r/min centrifuga 110min,leaving the upper serum-80℃ to be tested.Blood lipids,routine blood tests,blood biochemistry,brain natriuretic peptide(BNP)and echocardiography were routinely detected.The expression levels of serum Ub,26S proteasome and sST2 were detected by double antibody sandwich enzyme-linked immunosorbent assayResults:1.Comparison of general information:(1)There was no significant difference in WBC between the HF group and the control group(P>0.05).The NEUT%in the HF group was higher than that in the control group,and the difference was statistically significant(P<0.05).(2)The blood Crea and UREA in the HF group were higher than those in the control group,and the difference was statistically significant(P<0.05).(3)The levels of TC,TG,HDL and LDL in the heart failure group were significantly lower than those in the control group(P<0.05).(4)The left ventricular ejection fraction(LVEF)in the heart failure group was lower than that in the control group,and the difference was statistically significant(P<0.05).Interventricular septum thickness(IVST),left ventricular posterior wall diameter(LVPWd)and left ventricular end diastolic diameter(LVEDd)were significantly higher than those in the control group(P<0.05).2.Comparison of Ub,26S Proteasome and sST2 between HF and control grouP:(1)BNP,sST2,Ub and 26S proteasome levels in the HF group were higher than those in the control group,and the difference was statistically significant(P<0.05);(2)sST2 was correlated with LVEF and LVEDd,but not with LVPWd and IVST;(3)UB was correlated with LVEF and LVEDD,but not with LVPWD and IVST;(4)26 S Proteasome was correlated with LVEF and LVEDD,but not with LVPWD and IVST;(5)No correlation between sST2 and Ub,26S proteasome in HF group(6)The area under the ROC curve of Ub in the diagnosis of HF was 0.774(P<0.001),and the Cut-off value on the ROC curve was 219.79 ng/L,the sensitivity was 81.1%,and the specificity was 70.3%.The area under the ROC curve of 26S proteasome in the diagnosis of heart failure was 0.709(P<0.001),the Cut-off value on the ROC curve was 4815.29 ng/L,the sensitivity was 70.3%and the specificity was 67.6%Conclusion:(1)The elevated levels of Ub and 26S proteasome in serum of HF patients may be related to myocardial remodeling in HF patients;(2)Ub and 26S proteasomes are valuable in the diagnosis of HF(3)There was no correlation between sST2 and Ub,26S proteasome in patients with HF.