sST2 Concentrations Research Articles

Cerebrospinal fluid soluble growth stimulation expressed gene 2: A potential predictor of outcome for prognosis after aneurysmal subarachnoid hemorrhage

BackgroundSerum concentration of soluble growth stimulation expressed gene 2 (sST2) appears to have prognostic value in patients with aneurysmal subarachnoid hemorrhage (aSAH) by now. This study aimed to investigate the relationship between cerebrospinal fluid (CSF) sST2 concentration and outcome in patients with aSAH. MethodsA total of 65 aSAH patients who met the inclusion criteria in the Neurosurgery Department of Jining No.1 People's Hospital from March 2021 to August 2022 were selected as the research objects. 35 patients with the third month Modified-Rankin-Scale (mRS) score of 0–2 were divided into good prognosis group, and 30 patients with the third month mRS score of 3–5 were divided into poor prognosis group. CSF was collected by lumbar puncture for the first 5 days after aneurysm surgery. CSF sST2 concentration was determined using an enzyme-linked immunosorbent assay. ResultsIn all patients, CSF sST2 concentrations initially increased, peaked on day 2, and then decreased. Compared with the good prognosis group, the sST2 concentration was significantly increased in the poor prognosis group at 1, 2, 3, 4 and 5 days after aSAH surgery. CSF sST2 concentration exhibited good diagnostic performance for predicting outcome (area under the receiver operating characteristic curve = 0.988). Additionally, CSF sST2 concentration has good performance for predicting cerebral edema, but only in the poor prognosis group (area under the curve = 0.93). ConclusionsElevated CSF sST2 concentration is associated with poor outcome in aSAH patients. CSF sST2 may have a role as a predictive biomarker in these patients.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. During the median follow-up duration of 682days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P<0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1month, 3months, 1year and 2years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2ng/ml, 27.1ng/ml, 27.1ng/ml and 25.1ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

Correlations between soluble ST2 concentration and the nutritional status in patients with heart failure with reduced ejection fraction - cross-sectional study.

Heart failure (HF) is a global problem that stimulates research on markers associated with the diagnosis and course of the disease. Soluble suppression of tumorigenicity-2 (sST2) is a receptor for interleukin-33 and is associated with increased mortality rates in HF patients. Malnutrition in HF is also connected with inflammation and is associated with worse prognosis. The present study aimed to evaluate the relationship between sST2 concentration and the nutritional status of patients with HF with reduced ejection fraction (HFrEF). 138 patients with HFrEF were enrolled in this cross-sectional study. Nutritional status was assessed using Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT). The mean age was 53.6 ± 10.8 years. In the group with sST2 > 32.9 ng/mL, the GNRI score was higher and the associated risk of malnutrition was more common (29% vs. 12%; p = 0.011). Coherently in the group with sST2 > 32.9 ng/mL the median CONUT score was worse (2 [IQR 1-3] vs. 1 [IQR 0-2]; p = 0.0016) and the risk of malnutrition defined by this tool was also more prevalent (p = 0.0079). This relationship was independent of the concentration of natriuretic peptides, age and sex. According to available research, this research is the first study showing that sST2 concentration is related with nutritional status in HFrEF patients. sST2 may help to evaluate the necessity for nutritional intervention in HFrEF patients.

Soluble ST2 for predicting heart failure, atrial fibrillation and death in patients with coronary heart disease with or without renal insufficiency

BackgroundThis study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). MethodsBetween March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. ResultsAmong the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24–4.05), AF (HR: 2.86; 95%CI: 2.10–3.90), and death (HR:2.11, 95%CI: 1.67–2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. ConclusionsThe biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

Correlations of sST2 and Gal-3 with Cardiothoracic Ratio in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) frequently correlates with cardiovascular complications. Soluble suppression of tumorigenicity 2 (sST2) and Galectin-3 (Gal-3) are emerging as cardiac markers with potential relevance in cardiovascular risk prediction. The cardiothoracic ratio (CTR), a metric easily obtainable from chest radiographs, has traditionally been used to assess cardiac size and the potential for cardiomegaly. Understanding the correlation between these cardiac markers and the cardiothoracic ratio (CTR) could provide valuable insights into the cardiovascular prognosis of CKD patients. This study aimed to explore the relationship between sST2, Gal-3, and the CTR in individuals with CKD. Plasma concentrations of sST2 and Gal-3 were assessed in a cohort of 123 CKD patients by enzyme-linked immunosorbent assay (ELISA). On a posterior-to-anterior chest X-ray view, the CTR was determined by comparing the widths of the heart to that of the thorax. The mean concentration of sST2 in the study participants ranged from 775.4 to 4475.6 pg/mL, and the mean concentration of Gal-3 ranged from 4.7 to 9796.0 ng/mL. Significant positive correlations were observed between sST2 and the CTR (r = 0.291, p < 0.001) and between Gal-3 and the CTR (r = 0.230, p < 0.01). Our findings indicate that elevated levels of sST2 and Gal-3 are associated with an increased CTR in CKD patients. This relationship may enable better cardiovascular risk evaluation for CKD patients. Further studies are warranted to explore the clinical implications of these associations.

Associations Between Metabolic Syndrome, Ulcerative Colitis, and Fecal sST2 and CXCL8 Levels: Unveiling New Inflammatory Pathways

Abstract Ulcerative Colitis (UC), a chronic inflammatory bowel disease, exhibits complex interactions with metabolic disorders such as Metabolic Syndrome (MetS), which can significantly impact disease progression and patient outcomes. Among the multitude of players in this intricate network, soluble ST2 (sST2) and Chemokine (C-X-C motif) ligand 8 (CXCL8) have emerged as critical mediators of immune responses, potentially modulating the disease course in UC patients with co-existing MetS. This study aimed to investigate the association between Metabolic Syndrome (MetS) and immune response modulation in patients with Ulcerative Colitis (UC). UC patients, stratified by the presence of MetS, underwent clinical, endoscopic, and histological evaluation, along with blood and fecal biochemical analyses. Serum and fecal concentrations of sST2 and CXCL8 were measured and compared between groups. UC patients with MetS exhibited lower white blood cell (WBC) count, higher levels of metabolic markers, and milder disease severity on clinical, endoscopic, and histological scales. Serum concentrations of sST2 and CXCL8 were similar between UC patients with and without MetS. However, fecal levels of these cytokines were significantly elevated in UC patients with MetS, suggesting a localized intensified immune response. Our findings indicate a potential dichotomy in the immune response of UC patients with MetS, characterized by a dampened systemic inflammation and heightened local immune response. The elevated fecal levels of sST2 and CXCL8 underscore a potentially unique immune modulation within the gut in the presence of MetS. These findings shed new light on the pathophysiological interplay between MetS and UC and may provide new avenues for targeted therapeutic strategies.

Highly sensitive and specific graphene oxide-based FRET aptasensor for quantitative detection of human soluble growth stimulating gene protein 2

Soluble growth stimulation expressed gene 2 (sST2) is a new generation biomarker in the diagnosis and prognosis of heart failure (HF). Here, the sST2-specific aptamers were selected from a random ssDNA library with the full length of 88 nucleotides (nt) via target-immobilized magnetic beads (MB)-based systematic evolution of ligands by exponential enrichment (SELEX) technology. After eight rounds of selection, six aptamers with the most enrichment were selected. Among, the aptamer L1 showed the high-affinity binding to sST2 with the lowest Kd value (77.3 ± 0.05 nM), which was chosen as the optimal aptamer for further molecular docking. Then, the aptamer L1 was used to construct a graphene oxide (GO) - based fluorescence resonance energy transfer (FRET) biosensor for sST2, which exhibits a linear detection range of 0.1–100 μg/ml and a detection limit of 3.7 ng/ml. The aptasensor was applied to detect sST2 in real samples, with a good correlation and agreement with the traditional enzyme-linked immunosorbent assay (ELISA) when quantitative analyzing the sST2 concentration in serum samples from HF patients. The results show that not only an efficient strategy for screening the practicable aptamer, but also a rapid and sensitive detection platform for sST2 were established.

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) is characterized by high mortality and poor outcomes. This study aimed to explore the relationship between testosterone and soluble ST2 (sST2) and all-cause mortality in patients with SIC. Clinical data from SIC patients at Renmin Hospital of Wuhan University from January 2021 and March 2023 were reviewed. Serum testosterone and sST2 were measured at admission. Kaplan-Meier analysis and receiver operative characteristic curve (ROC) were used to estimate the predictive values of testosterone and sST2 on 28 days and 90 days mortality of SIC. A total of 327 male subjects with SIC were enrolled in this study. During the 28 days and 90 days follow-up, 87 (26.6%) and 103 deaths (31.5%) occurred, respectively. Kaplan-Meier analysis showed significantly higher 28 days and 90 days survival in patients with higher testosterone and decreased sST2 levels (p < 0.001). Testosterone, sST2, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were significantly associated with 28 days and 90 days mortality (p < 0.05). Partial correlation analysis showed strong positive correlation between testosterone and left ventricular ejection fraction (LVEF) (p < 0.001), and negative correlation between testosterone and sST2 (p < 0.001), high-sensitivity troponin I (hs-TnI) levels (p < 0.001) and smoke history (p < 0.01). The concentrations of sST2 were positively related with E/e' ratio (p < 0.001), and negatively correlated with TAPSE (p < 0.001). The combination of testosterone and sST2 enhanced the prediction of both 28 days [area under the ROC curve (AUC), 0.805] and 90 days mortality (AUC, 0.833). Early serum testosterone and sST2 levels could predict mortality of SIC independently and jointly. Further research is needed to determine the utility of biochemical markers in identifying high-risk patients with SIC.

Possibilities of predicting adverse cardiovascular events based on the analysis of clinical and instrumental research methods, as well as sST2 in patients after myocardial infarction

Aim: To determine the possibility of predicting adverse cardiovascular events based on the analysis of clinical and instrumental research methods, as well as sST2 in patients after myocardial infarction. Materials and Methods: The study included 64 patients who suffered an acute myocardial infarction and underwent PCI with balloon angioplasty and stenting of the infarct-related vessel in the acute period. The predictors of adverse cardiovascular events were assessed events during 1 year of observation. Indicators of echocardiography and coronary angiography were assessed and concentrations sST2. Results: A worse prognosis was associated with intermediate ejection fraction (EF) (odds ratio (OR)=3.981, p&lt;0.05), left aneurysm ventricle (LV) (OR=29.5, p&lt;0.05), high concentrations of sST2 (OR=1.017, p&lt;0.05) and scores on the Syntax scale (OR=1.001, p&lt;0.05). Conclusions: In patients who underwent percutaneous coronary intervention for myocardial infarction, adverse outcome during the next 2 years is associated with coronary and echocardiographic parameters, as well as biochemical indicators of myocardial stress and fibrosis. HF patients with intermediate EF, LV aneurysm, high sST2 concentrations, and high Syntax scores have the worst prognosis.

Soluble ST2 in Heart Failure: A Clinical Role beyond B-Type Natriuretic Peptide.

Soluble (s)ST2 has been proposed as a useful biomarker for heart failure (HF) patient management. Myocardial damage or mechanical stress stimulate sST2 release. ST2 competes with a membrane bound receptor (ST2 ligand, or ST2L) for interleukin-33 (IL-33) binding, inhibiting the effects induced by the ST2L/IL-33 interaction so that excessive sST2 may contribute to myocardial fibrosis and ventricular remodeling. Compared to natriuretic peptides (NPs), sST2 concentration is not substantially affected by age, sex, body mass index, kidney function, atrial fibrillation, anemia, or HF etiology, and has low intra-individual variation. Its prognostic role as an independent marker is well reported in the literature. However, there is a gap on its use in combination with NPs, currently the only biomarkers recommended by European and American guidelines for HF management. Reflecting the activation of two distinct biological systems, a benefit from the use of sST2 and NP in combination is advocated. The aim of this review is to report the current scientific knowledge on sST2 in the acute and chronic HF settings with a particular attention to its additive role to natriuretic peptides (NPs).

Soluble ST2, BCN-Bio-HF calculator and MAGGIC-HF score in long-term risk prediction after an urgent visit for heart failure.

Soluble ST2 (sST2) is the expression of a pathogenic process related to adverse remodeling that ultimately leads to increased mortality in heart failure (HF). Risk score models provide a comprehensive approach for mortality prediction, beyond the use of biomarkers alone. The objective was to determine the additional value of sST2 and two well-validated contemporary risk scores, BCN-Bio-HF and MAGGIC-HF, in predicting mortality and readmission in the acute setting. This prospective study included 129 patients (mean age 75 ± 9 years; 52% males) after an urgent HF visit. Baseline sST2 levels were measured and the two risk scores were calculated. The primary endpoint was all-cause mortality, and the secondary endpoint was HF readmissions. The follow-up period was 3.6 ± 1.9 years. Patients who died (46%) had higher sST2 concentrations (80.5 vs. 42.7 ng/ml; p < 0.001). The BCN-Bio-HF calculator with sST2 demonstrated the best discriminative ability for mortality prediction (area under the ROC curve: 0.792; p < 0.001). In multivariate analysis for each risk score, the MAGGIC-HF score retained its predictive value only in the model without sST2 (3-year risk: HR = 1.036; 95% CI 1.019-1.054; p < 0.001). However, the BCN-Bio-HF score maintained its prognostic value with sST2 (HR = 1.032; 95%CI 1.020-1.044; p < 0.001), as well as without sST2 (HR = 1.035; 95% CI 1.021-1.049; p < 0.001). sST2 was not associated with readmission, and only the BCN-Bio-HF risk of HF hospitalization showed independent predictive value (OR = 1.040; 95% CI 1.005-1.076; p = 0.023). For predicting long-term mortality in HF in the emergency department, the BCN-Bio-HF calculator with sST2 demonstrated superior discrimination and allows estimation of the risk of HF hospitalizations.

Importance of blood biomarker determination in the selection of patients with heart failure for cardioverterdefibrillator implantation

Aim. To conduct a comparative analysis of blood biomarker concentrations, to study their prognostic role in the occurrence of sustained ventricular tachyarrhythmia (VT) or VT episodes requiring electrotherapy in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤35% without prior syncope or sustained ventricular arrhythmias.Material and methods. This single-center prospective clinical study included 319 patients (men, 83%) aged 57 (51-63) years with LVEF of 29 (24-33)% receiving optimal therapy for HF, hospitalized for cardioverterdefibrillator implantation for the purpose of primary prevention of sudden cardiac death. Before the procedure, the concentration of blood biomarkers (blood electrolytes, C-reactive protein, creatinine, Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3) was determined. Based on blood creatinine concentration, glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients underwent a two-year prospective follow-up to record the end point of newly occurring clinically significant VT episodes detected by an implantable cardioverter-defibrillator.Results. The studied arrhythmic endpoint occurred in 84 (26,3%) patients. The multivariate analysis revealed three blood biomarkers, the concentration of which was associated with the first manifestation of VT. With sST-2 &gt;35 ng/ml, this risk increased by ~3 times (odds ratio (OR)=2,86; 95% confidence interval (CI): 1,23-6,64 (p=0,013)). Galectin-3 level &gt;12 ng/ml had a comparable prognostic value (OR=2,64; 95% CI: 1,06-6,53 (p=0,032)). In case of an increase in NT-proBNP &gt;2000 pg/ml, the risk of the same outcome was 2,2 times lower (OR=0,46; 95% CI: 0,22-0,95 (p=0,034)).Conclusion. Pre-implantation laboratory screening of NT-proBNP, sST-2 and galectin-3 concentrations can help in personalized assessment of arrhythmic risk in patients with HF and LVEF ≤35% referred for interventional primary prevention of sudden cardiac death.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19

BackgroundSoluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. MethodssST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. Results495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6–83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3–97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. ConclusionssST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies.

Linggui Zhugan decoction delays ventricular remodeling in rats with chronic heart failure after myocardial infarction through the Wnt/β-catenin signaling pathway

ContextTraditional Chinese medicine plays an important role in the prevention and treatment of heart failure (HF). Linggui Zhugan decoction has been approved for clinical treatment of chronic HF. However, the mechanism is still unclear. ObjectiveThe effect of Linggui Zhugan decoction on the Wnt/β-catenin signaling pathway in rat myocardium was studied to investigate the mechanism by Linggui Zhugan decoction effects ventricular remodeling in rats with heart failure after myocardial infarction. MethodA rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery. After 6 weeks of intervention with Linggui Zhugan decoction, the effect of Linggui Zhugan decoction on the cardiac function of chronic HF model rats was observed. Myocardial infarct size was measured by triphenyl tetrazolium chloride (TTC) staining. Enzyme linked immunosorbent assays (ELISAs) were used to measure NT-proBNP and sST-2 concentrations in rat serum. Hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were used to observe the morphology of myocardial tissue; immunohistochemistry was used to detect the protein expression of type I collagen and type III collagen in myocardial tissue; and mRNA expression levels of Wnt3a, GSK-3β, β-catenin, and c-Myc in the infarct marginal zone were detected using PCR. Protein expression of Wnt3a, p-GSK-3β, GSK-3β, and β-catenin in the infarct marginal zone was detected using western blot. ResultsCompared with the control, Linggui Zhugan decoction reduced the levels of serum ST-2 and NT-proBNP, improved cardiac function, and reduced the deposition of collagen fiber. In addition, Linggui Zhugan decoction inhibited the expression of Wnt3a, p-GSK-3β, and β-catenin in cardiomyocytes. ConclusionLinggui Zhugan decoction inhibits the expression of several key proteins in the Wnt/β-catenin signaling pathway, delays cardiomyocyte hypertrophy and fibrosis, and improves cardiac function.

Circulating Gal-3 and sST2 are associated with acute exercise-induced sustained endothelial activation: Possible relevance for fibrosis development?

Long-term, intense endurance exercise training can occasionally induce endothelial micro-damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well-trained male participants (10runners and 10cyclists) performed a strenuous high-intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal-3 and sST2 concentrations were investigated by enzyme-linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal-3 and sST2 concentrations and ECs were elevated after exercise (P<0.001), without interaction between exercise modalities. Circulating Gal-3 and sST2 concentrations both showed a positive relationship with ECs (rrm =0.68, P=0.001 and rrm =0.57, P=0.010, respectively, both n=18). The EC association with Gal-3 was significant only in cyclists, but equally strong for both modalities. Gal-3 was also related to exercise-induced CTi (rrm =0.57, P=0.011, n=18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise-released Gal-3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise-induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long-term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. NEW FINDINGS: What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal-3 is an enhanced cardiac contractility. Acute exercise-released Gal-3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation.

Resveratrol is an organic compound widely studied for its therapeutic uses. We investigated whether resveratrol exerts cardioprotective effects by inhibiting ferroptosis via the Sirt1/p53 pathway. A heart failure model was established by aortic coarctation in Sirt1 knockout mice. The superoxide dismutase (SOD), glutathione (GSH) levels and mitochondrial morphology in murine heart tissues were assessed at different time points to determine the role of ferroptosis in heart failure progression. The cardiac function of mice with heart failure was evaluated by determining the brain natriuretic peptide (BNP) and sST2 concentration and conducting echocardiography. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were transfected with the p53 K382R mutant and Sirt1 interference lentiviral vectors. Immunoprecipitation (IP) experiments were performed to investigate whether Sirt1 influences ferroptosis via p53 K382 acetylation and SLC7A11 expression modulation. Resveratrol improved cardiac function in mice and decelerated ferroptosis and fibrosis progression in heart failure. However, the ability of resveratrol to prevent ferroptosis and treat heart failure was lost after silencing Sirt1. Sirt1 reduced ferroptosis by diminishing the levels of p53 K382 acetylation, reducing the degradation of SLC7A11, and increasing the levels of GSH and glutathione peroxidase 4 (GPX4) in cells. In conclusion, by activating the Sirt1/p53 pathway in heart failure, resveratrol decreased the depletion of SLC7A11, inhibited ferroptosis, and improved cardiac function.

SST2 and NT-proBNP biomarkers in prediction of COVID-19

Background. COVID-19 may cause or worsen cardiac dysfunction and patients with pre-existing cardiovascular disease, including heart failure (HF), who have an increased risk of severe and fatal outcomes of COVID-19. The study aimed to determine the role of soluble suppression of tumorigenesis-2 protein (sST2) and natriuretic peptide test (NT-proBNP) in predicting the severe course and in-hospital mortality of patients with COVID-19 and hypertension. Materials and methods. One hundred and fifteen patients with COVID-19 and hypertension were examined. The determination of sST2 and NT-proBNP in blood serum were done using the enzyme-linked immunosorbent assay. The clinical endpoint was assessed during the hospitalization period (death, hospitalization in the intensive care unit, prolonged hospitalization). The risk of the final event development was calculated for the patients who reached the threshold sST2 concentrations, and, separately, based on the diagnostic values of the NT-proBNP. Results. The cut-off values of sST2 recommended for the diagnosis of HF in our study were reached in 7 (28 %) cases. The risk of final clinical points development in these patients was as follows: OR = 10.67; 95% CI: 1.31–86.9; p = 0.0270. The level of NT-proBNP, which meets the criteria for the diagnosis of HF, was constant in only 10 (11.1 %) individuals (p = 0.0461) and the risk of clinical events developing was equal to OR = 7.0; 95% CI: 1.72–28.6; p = 0.0067. Conclusions. Stratification of patients based on sST2 values, in addition to NT-proBNP parameters, may provide further prognostic value compared to NT-proBNP levels in patients with COVID-19 and HF.

SST2 Levels Show No Association with Helicobacter pylori Infection in Asymptomatic Patients: Implications for Biomarker Research

IntroductionHelicobacter pylori (H. pylori) is a prevalent stomach bacterium that can cause a range of clinical outcomes, including gastric cancer. In recent years, soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer. The purpose of this study was to explore the possible connection between H. pylori infection and sST2 levels in patients who do not exhibit symptoms.MethodsA total of 694 patients from the Salzburg Colon Cancer Prevention Initiative (Sakkopi) were included in the study. The prevalence of H. pylori infection was determined by histology, and sST2 levels were measured in serum samples. Clinical and laboratory parameters, such as age, sex, BMI, smoking status, hypertension, and metabolic syndrome, were also collected.ResultsThe median sST2 concentration was similar between patients with (9.62; 7.18–13.44 ng/mL; p = 0.66) and without (9.67; 7.08–13.06 ng/mL) H. pylori. Logistic regression analysis did not show any association (OR 1.00; 95%CI 0.97–1.04; p = 0.93) between sST2 levels and H. pylori infection, which remained so (aOR 0.99; 95%CI 0.95–1.03; p = 0.60) after adjustment for age, sex, educational status, and metabolic syndrome. In addition, sensitivity analyses stratified by age, sex, BMI, smoking status, educational status, and the concomitant diagnosis of metabolic syndrome could not show any association between sST2 levels and H. pylori infection.ConclusionThe results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection. Our findings are of relevance for further research investigating sST2, as we could not find an influence of asymptomatic H. pylori infection on sST2 concentration.What Is Already Known?Soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer.What Is New in This Study?The median sST2 concentration was similar between patients with (9.62; 7.18–13.44 ng/mL; p = 0.66) and without (9.67; 7.08–13.06 ng/mL) H. pylori.What Are the Future Clinical and Research Implications of the Study Findings?The results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection.

#5690 COMBINED USE OF SOLUBLE ST2 AND NT-PROBNP FOR PREDICTING MAJOR ADVERSE CARDIOVASCULAR EVENTS IN TYPE 2 DIABETES AND DIVERSE RENAL FUNCTION

Abstract Background and Aims Plasma levels of soluble ST2 protein (sST2), a biomarker associated with fibrosis and inflammation, have been related with an increased risk of adverse events in patients with heart failure (HF) [1,2]; however, data is limited on the prognostic value of sST2 in patients with type 2 diabetes mellitus (T2DM) [3], particularly in association with chronic kidney disease (CKD)4. We aimed to evaluate the impact on cardiovascular (CV) prognosis of sST2 in a population of T2DM with diverse renal function. Method A prospective observational study was conducted in patients with T2DM. Demographic, clinical and analytical data were collected. The main objective was to analyze a composite of combined CV events (major adverse cardiovascular events; MACE) including: CV death, acute myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, atrial fibrillation, significant valvular heart disease, and hospitalization for any other CV cause). The levels of sST2 and NT-proBNP were analyzed in association with the primary endpoint, as well as with each event separately by survival analysis (log-rank test). Results Ninety-three patients were included with a mean follow-up of 3.5 (3.4-4.2) years. Median sST2 concentrations were 29.8 ng/mL. Table 1 shows the baseline characteristics of patients according to sST2 levels. Univariate analysis showed that higher sST2 levels independently predicted the occurrence of MACE (HR = 2.92; 95% CI: 1.35-6.33) (Figure 1). These results persisted after adjusting for age, sex, and glomerular filtration rate. In addition, a significant interaction was found between sST2 and NT-proBNP, showing a significant relationship between the combination of both biomarkers and the main event (Figure 1). Conclusion Elevated sST2 levels are associated with the occurrence of long-term major cardiovascular events in patients with T2DM, independently of renal function. These findings could allow stratification of patients with T2DM according to their cardiovascular risk in order to develop therapeutic strategies based on precision medicine.

Sensitive Electrochemical Immunosensor Based on MXene-Nafion/Polyaniline (PANI) for the Sensitive Determination of the Novel Biomarker sST2 for Atherosclerotic Coronary Heart Disease by Differential Pulse Voltammetry (DPV)

Atherosclerotic coronary heart disease (CHD) is ischemic and a worldwide health issue. The soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker for atherosclerotic coronary heart disease. This work develops an immunosensor with a nanocomposite consisting of polyaniline (PANI) and MXene-Nafion for the specific and sensitive determination of sST2. PANI was first electropolymerized on a glassy carbon electrode (GCE) to enhance electron transfer. Subsequently, MXene-Nafion dispersion was drop cast on the PANI/GCE substrate to further increase the electrical conductivity and immobilize anti-sST2 which captures sST2 for detection. The current response as a function of sST2 concentration was measured by differential pulse voltammetry (DPV). Under the optimal conditions, this immunosensor demonstrates a linear range from 1 pg mL−1 to 1 μg mL−1 and a detection limit of 0.149 pg mL−1. The device offers high sensitivity, excellent specificity, satisfactory reproducibility, good stability, and has significant potential for detecting clinical biomarkers. In addition, the immunosensor is able differentiate between serum of healthy people and CHD patients.