Correlation of serum ST2 levels with severity of diastolic dysfunction on echocardiography and findings on cardiac MRI in patients with heart failure with preserved ejection fraction

Objective: The aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients. Methods: Fifty patients aged _x0001_18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E’, left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI. Results: ST2 levels showed statistically significant and positive correlation with E/E’ (r ¼ 0.837), peak TR velocity (r ¼ 0.373), LAVI (r ¼ 0.74), E/A (r ¼ 0.420), and T1 values in milliseconds (r ¼ 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r ¼ 0.145). The median ST2 levels in patients with E/E’ > 14 and E/E’ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3). Conclusions: Evaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF

Evaluation of Serum Interleukin-33 and Soluble Suppression of Tumorigenicity 2 (sST2) Receptors in Patients with and without Periodontal Disease

Context: Interleukin?33 and its receptor soluble suppression of tumorigenicity 2 (sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both IL?33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: To assess the levels of IL?33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross?sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL?33 and sST2 were determined by the enzyme?linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: The level of IL?33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL?33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL?33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL?33 and sST2 in periodontitis patients. IL?33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL?33 and sST2 together among patients with and without periodontal disease.

Effect of Xiao Qinglongtang on IL-33/ST2 Signaling Pathway in Mice with Allergic Rhinitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.

Clinical study on diagnosis of myocardial fibrosis by soluble suppression of tumorigenicity 2, galectin-3 combined with magnetic resonance multimodality / 中国医师进修杂志

Objective:To explore the application value of soluble tumor suppressor 2 (SST2), galectin-3 combined with magnetic resonance multimodality in the diagnosis of myocardial fibrosis.Methods:The clinical data of 88 patients with cardiomyopathy from January 2017 to December 2019 in Handan Central Hospital of Hebei Province were retrospectively analyzed as the experimental group, and 100 healthy people in the same period were selected as the control group. According to the results of cardiac magnetic resonance imaging (CMRI)-late gadolinium enhanced (LGE), the patients with cardiomyopathy were divided into LGE positive and LGE negative. The arrhythmia rate was evaluated by ambulatory electrocardiogram. The New York Heart Association (NYHA) cardiac function grade was recorded. The left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were detected by echocardiography. The SST2, galectin-3 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of SST2 and Galectin-3 in predicting myocardial fibrosis in patients with cardiomyopathy.Results:CMRI-LGE results of 88 patients with cardiomyopathy showed that LGE was positive in 42 cases and negative in 46 cases. The arrhythmia rate, LVEDD, SST2 and galectin-3 in experimental group were significantly higher than those in control group: 67.05% (59/88) vs. 2.00% (2/100), (46.55 ± 5.99) mm vs. (27.92 ± 2.05) mm, (61.83 ± 10.57) μg/L vs. (24.99 ± 7.69) μg/L and (18.65 ± 3.39) μg/L vs. (7.12 ± 1.33) μg/L, the LVEF was significantly lower than that in control group: (55.11 ± 8.36)% vs. (68.83 ± 9.45)%, and there were statistical differences ( P<0.01). The arrhythmia rate, NYHA cardiac function grade, LVEDD, SST2 and galectin-3 in patients with LGE positive were significantly higher than those in patients with LGE negative: 88.10% (37/42) vs. 47.83% (22/46), (3.10 ± 0.53) grade vs. (2.11 ± 0.61) grade, (48.88 ± 5.95) mm vs. (44.41 ± 5.24) mm, (65.58 ± 11.73) μg/L vs. (58.40 ± 8.10) μg/L and (21.00 ± 2.72) μg/L vs. (16.51 ± 2.39) μg/L, the LVEF was significantly lower than that in patients with LGE negative: (52.15 ± 8.23)% vs. (57.82 ± 7.60)%, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the optimal critical values of serum SST2 and galectin-3 for predicting myocardial fibrosis in patients with cardiomyopathy were 65.07 μg/L and 18.46 μg/L, the area under the curve was 0.714 (95% CI 0.604 to 0.825, P = 0.001) and 0.894 (95% CI 0.828 to 0.960, P = 0.001), the sensitivity was 61.9% and 85.7%, and the specificity was 80.4% and 82.6%. Conclusions:Magnetic resonance multimodality has a good ability in detecting myocardial fibrosis, and serum SST2 and galectin-3 have good predictive value for myocardial fibrosis. SST2 and galectin-3 combined with magnetic resonance multimodality has important clinical significance in the diagnosis of myocardial fibrosis.

Dual role of interleukin-33 in tumors / 中南大学学报(医学版)

Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.

The level and clinical significance of soluble ST2 in heart failure patients with atrial fibrillation / 中华检验医学杂志

Objective@#To determine the level of Soluble Suppression of Tumorigenicity-2 (sST2) in patients with heart failure(HF) and atrial fibrillation (AF), and to explore its diagnostic and prognostic value in patients with HF and AF.@*Methods@#A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital. And according to whether they had atrial fibrillation before admission, we categorized patients into: HF with sinus rhythm (HF-SR, n=90) and HF with AF(HF-AF, n=95). Meanwhile, 40 healthy controls were collected. Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared. Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA). Statistical methods such as nonparametric test and Spearman correlation analysis were used. The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups. And by using the COX risk model, Multi-factor COX analysis was used to analyze the prognosis of patients.@*Results@#Compared with healthy controls, the median (P25, P75) of Plasma sST2 levels in HF patients increased remarkably [32.93 (20.31-51.39) ng/mL vs 15.99(7.97-22.69) ng/mL, Z=-4.373, P<0.001]. Patients with HF-AF group had significantly higher test results [39.86 (27.20-59.21)] ng/mL than HF-SR group [24.74 (14.83-44.11)] ng/mL, Z=-6.783, P<0.001].In the HFmrEF and HFpEF subgroups, the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group (Z=-2.381, P=0.017; Z=-3.701, P<0.001).Spearman correlation analysis showed that, in HF-AF patients, plasma sST2 level was positively correlated with diastolic blood pressure, Hypertension, New York Association (NYHA) cardiac function classification Ⅲ to Ⅳ, white blood count(WBC), and the level of Alanine Aminotransferase (ALT), Υ-glutamine transaminase (Υ-GT), B-type natriuretic peptide (BNP) (r>0, P<0.05).Also, there is a negative correlation between sST2, left ventricular ejection fraction (LVEF) and estimated Glomerular Filtration Rate (eGFR) (r<0, P<0.05). At ROC analysis, sST2 showed predictive value in both HF-AF and HF-SR group, with an optimal cut-off value of 25.33 ng/mL(AUC 0.872, 95%CI: 0.805-0.935, P<0.001, sensitivity 81.1%, specificity 87.5%) and 23.34 ng/mL(AUC 0.665, 95%CI: 0.570-0.761, P<0.001, sensitivity 55.6%, specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699, respectively, and the AUC of sST2 was higher than that of BNP. Multi-factor COX analysis indicated that plasma sST2 level, BNP, NYHA cardiac function grading could be risk factors for cardiac events in HF patients. Plasma sST2, left atrial diameter (LA-D), and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF. The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL (χ2=7.625, P=0.006). The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL (χ2=4.287, P=0.038).@*Conclusions@#The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls. The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR. It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR, HF-AF than BNP. HF-AF Patients with plasma sST2 ≥ 39.86 ng/mL are prone to cardiovascular events.

Effect of high-sensitivity cardiac troponin Ⅰ and soluble suppression of tumorigenicity 2 in acute organophosphorus pesticide poisoning / 中华急诊医学杂志

Objective To study the early diagnostic value of high-sensitivity cardiac troponin Ⅰ(hs-cTnI) and soluble growth stimulating gene 2 protein (soluble suppression of tumorigenicity 2,sST2) in myocardial injury of acute organophosphorus pesticide poisoning (AOPP).Methods Totally 168 AOPP patients hospitalized from March 2014 to October 2018 were divided into the mild group (n=45),moderate group (n=55) and severe group (n=68).Another 30 healthy persons were served as the control group.The levels of cTnI,hs-cTnI,N-terminal B-type natriuretic peptide(NT-proBNP) and sST2 were detected at 4 h and 12 h after admission.SPSS 21.0 was used for statistical analysis.The measurement data were expressed by mean±standard deviation,two groups were compared by LSD-t test,and the multigroup comparison was made by single factor analysis of variance (ANOVA).The correlation analysis by Spearman correlation test (P＜0.05).Results At 1 h after admission,the hs-cTnI of AOPP patients with different degrees of poisoning was higher than that of control group,and that of severe group was higher than that of mild to moderate group.Comparison between groups was statistically significant (P＜0.05).However,there was no significant difference in the cTnI level (P＞0.05).At 4 h and 12 h after admission,the levels of cTnI and hs-cTnI increased with the increase of poisoning degree and the extension of time,and their level at 12 h after admission were significantly higher than those at 4 h after admission,with statistically significant difference between the two groups (P＜0.05).At 1 h after admission,the level of sST2 in the poisoned patients was higher than that in the control group,and the level in the severe group was higher than that in the mild to moderate groups.At 4 h and 12 h after admission,the level of sST2 was increased significantly,especially in the severe group.The level of sST2 at 12 h after admission was significantly higher than that at 4 h after admission (P＜0.05).The concentration of NT-proBNP was in normal range 1 h after admission,increased gradually at 12 h after admission,and the level of NT-proBNP in the severe group was significantly higher than that in the other groups (P＜0.05),and comparison between the groups was significantly different (P＜0.05).The correlation analysis showed that there was a positive correlation between hs-TnI and sST2 in AOPP patients (r=0.776,P＜0.01).hs-TnI and sST2 was positively correlated with the severity of AOPP (r=0.958,P＜0.01;r=0.844,P＜0.01).That is,the more severe the patient,the higher the concentration of hs-TnI and sST2,and the more serious myocardial injury.Conclusions Early detection ofhs-cTnI and sST2 levels in AOPP patients can identify early myocardial damage and objectively evaluate the extent of myocardial damage.

Assessment for the Diagnostic Value of Soluble Suppression of Tumorigenicity-2 in Heart Failure by Meta-analysis / 中国循环杂志

Objective: To assess the diagnostic value of soluble suppression of tumorigenicity-2 (sST2) in heart failure (HF) by Meta-analysis. Methods: We searched the databases of CNKI, Wei Pu, CBMdisc,WanFang and Pubmed up to 2017-03-14 for diagnostic value of sST2 in HF patients. Corresponding references were enrolled and relevant data was extracted. Quality evaluation was conducted by quality assessment of diagnostic accuracy studies-2(QUADAS-2)method, effect of sST2 in HF diagnosis was analyzed by Stata14.0 and Revman software. Results: A total of 13 references were eligible including 5 English and 8 Chinese. Meta analysis showed that the diagnostic value of sST2 in HF had the pooled sensitivity at 79%, 95% CI (0.68-0.86);pooled specificity at 69%, 95% CI (0.58-0.79); positive like hood rate was 2.57, 95% CI(1.86-3.53), negative like hood rate was 0.31, 95%CI (0.21-0.46), diagnostic odds rate was 8.28, 95% CI (4.76-14.42); the area under ROC was 0.8. Deek's funnel plot demonstrated no publication bias in Meta-analysis. Conclusion: sST2 had moderate value in diagnosing HF; duo to the defect in methodology, large sample, scientific and reasonable random controlled trails should be conducted to confirm the diagnostic efficacy.

Prognostic Role of High-sensitivity Cardiac Troponin I and Soluble Suppression of Tumorigenicity-2 in Surgical Intensive Care Unit Patients Undergoing Non-cardiac Surgery

BACKGROUND: The prognostic utility of cardiac biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity-2 (sST2), in non-cardiac surgery is not well-defined. We evaluated hs-cTnI and sST2 as predictors of 30-day major adverse cardiac events (MACE) in patients admitted to the surgical intensive care unit (SICU) following major non-cardiac surgery. METHODS: hs-cTnI and sST2 concentrations were measured in 175 SICU patients immediately following surgery and for three days postoperatively. The results were analyzed in relation to 30-day MACE and were compared with the revised Goldman cardiac risk index (RCRI) score. RESULTS: Overall, 30-day MACE was observed in 16 (9.1%) patients. hs-cTnI and sST2 concentrations differed significantly between the two groups with and without 30-day MACE (P < 0.05). The maximum concentration of sST2 was an independent predictor of 30-day MACE (odds ratio=1.016, P=0.008). The optimal cut-off values of hs-cTnI and sST2 for predicting 30-day MACE were 53.0 ng/L and 182.5 ng/mL, respectively. A combination of hs-cTnI and sST2 predicted 30-day MACE better than the RCRI score. Moreover, 30-day MACE was observed more frequently with increasing numbers of above-optimal cut-off hs-cTnI and sST2 values (P < 0.0001). Reclassification analyses indicated that the addition of biomarkers to RCRI scores improved the prediction of 30-day MACE. CONCLUSIONS: This study demonstrates the utility of hs-cTnI and sST2 in predicting 30-day MACE following non-cardiac surgery. Cardiac biomarkers would provide enhanced risk stratification in addition to clinical RCRI scores for patients undergoing major non-cardiac surgery.

IL-33/ST2 axis in systemic lupus erythematosus in relation to chronic kidney injury and disease activity / 中国病理生理杂志

AIM:To elucidate the association between chronic kidney injury and interleukin-33 (IL-33;an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS:Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS:The levels of IL-33 and sST2,and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC.The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI),erythrocyte sedimentation rate (ESR),proteinuria and triglyceride,but negatively associated with complement C3.IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR).Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R2 =0.442),especially CKD staging.CONCLUSION:Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury.IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.

IL-33/ST2 axis in systemic lupus erythematosus in relation to chronic kidney injury and disease activity / 中国病理生理杂志

AIM:To elucidate the association between chronic kidney injury and interleukin-33 (IL-33;an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS:Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS:The levels of IL-33 and sST2,and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC.The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI),erythrocyte sedimentation rate (ESR),proteinuria and triglyceride,but negatively associated with complement C3.IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR).Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R2 =0.442),especially CKD staging.CONCLUSION:Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury.IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.

Soluble ST2 Has a Prognostic Role in Patients With Suspected Sepsis

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) has emerged as a novel biomarker for heart failure, and serum sST2 concentrations could be increased in inflammatory diseases. We explored whether sST2 is related to cardiac dysfunction/failure and has a prognostic role in patients with suspected sepsis. METHODS: In a total of 397 patients with suspected sepsis, sST2 concentrations were measured by using the Presage ST2 Assay (Critical Diagnostics, USA). sST2 concentrations were analyzed according to procalcitonin (PCT) concentrations, cardiovascular subscores of the sepsis-related organ failure assessment (SOFA) score, and clinical outcomes. RESULTS: sST2 concentrations were increased significantly according to the five groups of PCT concentrations and cardiovascular subscores of the SOFA score (P<0.000001 and P=0.036, respectively). In-hospital mortality was significantly higher among patients with sST2 concentrations above 35 ng/mL (P=0.0213) and among patients with increased concentrations of both sST2 and PCT (P=0.0028). CONCLUSIONS: sST2 seems to be related to both cardiac dysfunction/failure and severity in sepsis. Measurement of sST2 and PCT in combination would be useful for risk stratification and prognosis prediction in patients with suspected sepsis.