Are soluble ST2 levels influenced by vitamin D and/or the seasons?
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ABSTRACT: Objective
Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability.Design
sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design).
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PROVIDER: S-EPMC6528407 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Are soluble ST2 levels influenced by vitamin D and/or the seasons?
Endocrine connections 20190601 6
<h4>Objective</h4>Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability.<h4>Design</h4>sST2 levels were measured in two cohorts involving hypertensiv ...[more]
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Project description:BackgroundSevere leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis.Methodology and principal findingsIn an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2-3.6) and severe bleeding (OR 5.1; 95%CI: 1.1-23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0-5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected.ConclusionsPatients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. In vitro experiments showed that (white) blood cells are probably not the source. In this regard, sST2 could be an indicative marker for tissue damage in patients suffering from severe leptospirosis.
| S-EPMC2684584 | biostudies-literature
Project description:Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior.
| S-EPMC7216579 | biostudies-literature
Project description:BackgroundAlthough the role of vitamin D receptor (VDR) in muscle mass and strength is well established, the effects of vitamin D (VD) on muscle remain controversial due to various factors. Herein, the influence of sex on the effects of VD on muscle function and the underlying reasons was explored.MethodsMale and female Sod1 gene knockout (SKO) mice, serving as a model for skeletal muscle atrophy, were treated with the VD active analogue calcipotriol, and RNA sequencing was employed to investigate this potential signalling pathway. The National Health and Nutrition Examination Survey (NHANES) database was utilized to explore whether testosterone affects the correlation between VD and grip strength in human participants. Experiments involving C2C12 cells and castrated male mice subjected to immobilization were conducted to demonstrate the enhancing effects of testosterone on VD function.ResultsIn male SKO mice, Vdr expression in the gastrocnemius muscle was positively correlated with grip strength (R2 = 0.4689, p < 0.001), whereas no such correlation was identified in female mice. At 28 weeks of age, both male and female SKO mice exhibited significantly reduced grip strength compared to Sod1 wild-type (SWT) mice, and calcipotriol restored grip strength in male SKO mice (SWT-veh: 0.0716 ± 0.0006, SWT-cal: 0.0686 ± 0.0010, SKO-veh: 0.0601 ± 0.0010, SKO-cal: 0.0703 ± 0.0007; p < 0.05). Calcipotriol increased muscle protein synthesis and mitochondrial biogenesis while decreasing inflammation and atrogenes in gastrocnemius muscle of male SKO mice. However, the effect of calcipotriol on muscle was not significant in female SKO mice. Compared to wild-type mice, both male and female SKO mice exhibited reduced levels of 1,25(OH)2D3 due to ROS-induced hepatic CYP3A4 overexpression, thereby excluding the influence of baseline VD levels. The serum 25(OH)D3 and testosterone interactively affect grip strength in adults (p < 0.05). Using C2C12 cells differentiated into myotubes, testosterone significantly enhanced the inducing effects of VD on VDR, androgen receptor (AR), P-AKT, PGC1α, Beclin1 and LC3B. Calcipotriol improved grip strength in sham-operated mice but had a negligible effect on grip strength in castrated mice. However, a significant improvement in grip strength was observed in castrated mice following testosterone restoration (p < 0.05).ConclusionsThis study demonstrates the existence of sex heterogeneity in the effects of VD on muscle and that testosterone enhances the strength and molecular responses to VD. These findings underscore the importance of considering testosterone levels when utilizing VD to enhance muscle strength.
| S-EPMC11830628 | biostudies-literature
Project description:IntroductionSupplementation of water-soluble vitamins is a common practice in hemodialysis patients, but dosages are largely based on conventional hemodialysis techniques. The aim of this study was to assess the status of water-soluble vitamins in patients on hemodiafiltration (HDF), and attempt to determine optimal dose of vitamin supplements.MethodsThis monocentric study included 40 patients on thrice-weekly chronic HDF. At baseline, all patients received 2 tablets of Dialvit containing B and C vitamins after each dialysis session. Predialysis samples of B and C vitamins were measured in both blood (n = 40) and a subgroup of dialysate (n = 6) samples. A second blood sample was obtained in 24 patients 3 months after dose adjustment of the vitamin supplement.ResultsAt baseline, B-vitamin levels were high with, respectively, 0.4%, 10.0%, and 89.6% of patients in the low, normal, and high reference range. For vitamin C, most patients were in the normal range (5.0%, 82.5%, and 12.5% in low, normal, and high reference range). Three months after dose reduction, B vitamin levels decreased but stayed mostly at or above the normal range (1.4%, 25.7%, 72.9% in low, normal, and high reference range). Three patients (12.5%) developed vitamin C deficiency on low-dose substititon.ConclusionThis study shows that the levels of most vitamins are above the normal range in patients on HDF receiving a classic dose of vitamin supplements, vitamin C excepted. Our study suggests that the classic dose of postdialysis vitamin B supplements may be reduced.
| S-EPMC7710883 | biostudies-literature
Project description:BackgroundMurine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway.MethodsWe assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malaria (CM, n=224) or severe malarial anemia (SMA, n=193).ResultsPlasma concentrations of sST2 were higher in children with CM than in children with SMA or in asymptomatic community children. Cerebrospinal fluid (CSF) sST2 levels were elevated in children with CM compared with North American children. Elevated plasma and CSF ST2 levels in children with CM correlated with increased endothelial activation and increased plasma and CSF levels of tau, a marker of neuronal injury. In children with CM who were ≥5 years of age at the time of their malaria episode, but not in children <5 years of age, elevated risk factor-adjusted plasma levels of sST2 were associated with worse scores for overall cognitive ability and attention over a 2-year follow-up.ConclusionsThe study findings suggest that sST2 may contribute to neuronal injury and long-term neurocognitive impairment in older children with CM.
| S-EPMC9254869 | biostudies-literature
Project description:IntroductionCardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD).MethodsThis was a pooled analysis of 2 longitudinal cohorts of participants with CKD: the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS). We measured circulating concentrations of sST2 and galectin-3 at baseline. Our primary outcome was progression to estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m2 or end-stage renal disease (ESRD). We used competing risk Cox regression models to study the association of sST2 and galectin-3 with CKD progression, adjusting for demographics, kidney function, and comorbidity.ResultsAmong the 841 participants in the pooled cohort, baseline eGFR was 51 ± 27 ml/min per 1.73 m2 and median urine albumin-to-creatinine ratio (UACR) was 141 (interquartile range = 15-736) mg/g. Participants with higher sST2 and galectin-3 were more likely to be older, to have heart failure and diabetes, and to have lower eGFR. Adjusting for demographics, kidney function, and comorbidity, every doubling of sST2 was not associated with progression to eGFR <15 ml/min per 1.73 m2 or ESRD (adjusted hazard ratio 1.02, 95% confidence interval = 0.76-1.38). Every doubling of galectin-3 was significantly associated with a 38% (adjusted hazard ratio = 1.35, 95% confidence interval = 1.01-1.80) increased risk of progression to eGFR <15 ml/min per 1.73 m2 or ESRD.ConclusionHigher concentrations of the cardiac biomarker galectin-3 may be associated with progression of CKD, highlighting potential novel mechanisms that may contribute to the progression of kidney disease.
| S-EPMC6308819 | biostudies-literature
Project description:BackgroundThe soluble forms of suppression of tumorigenicity-2 (ST2) and galectin-3 have been proposed as novel biomarkers for cardiac fibrosis and heart failure, as well as predictors of cardiovascular events and mortality. However, there are limited data on the association between soluble ST2 and galectin-3 and clinical outcomes in patients with kidney failure on replacement therapy. To determine this, we examined the associations between soluble ST2 and galectin-3 and all-cause mortality and cardiovascular events in patients on hemodialysis.MethodsThis study included maintenance hemodialysis patients (over 18 years old) who consented to preserve their serum in the Biobank at our institution between March 2014 and March 2015. We used Cox proportional hazards regression analysis to evaluate the associations between soluble ST2, galectin-3 levels, and clinical outcomes. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease, and patients were followed for both outcomes until March 2018.ResultsA total of 296 patients were analyzed in this study. The mean age was 57 ± 13 years, and 53.0% were male. Serum concentration of soluble ST2 was significantly associated with higher mortality, after adjustment for confounding factors, but was not associated with cardiovascular disease. Serum galectin-3 level was not independently associated with either outcome after adjustment.ConclusionElevated soluble ST2 is independently associated with an increased risk of mortality, but not with cardiovascular disease, in patients on hemodialysis. Elevated galectin-3 was not associated with mortality or cardiovascular disease.
| S-EPMC8041640 | biostudies-literature
Project description:BackgroundSevere dengue virus (DENV) infection involves plasma leakage and vascular collapse, and leads to significant morbidity and death. Serum soluble ST2 (sST2 [interleukin (IL)-1 receptor like-1 protein: IL-1-RL-1]) levels are high in pediatric cases of DENV infection, and the disease progresses. However, the correlation between serum sST2 levels and the outcomes of DENV infection in the elderly (≥65 years) is unclear. We thus explored the mechanisms of serial sST2 level changes involved in the coagulopathy and bloodstream infections of elderly patients in Taiwan's 2015 DENV outbreak.MethodsThis retrospective study was done in a tertiary medical center in southern Taiwan during the outbreak. All DENV-infected patients who, between July 1, 2015, and December 31, 2015, provided a written informed consent for at least two blood sample analyses were enrolled and reviewed. The serum levels of sST2 were quantified. ΔsST2 is defined as the "changes of sST2 levels in serially paired samples". Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) analyses were used to evaluate the prognostic ability of ΔsST2.ResultsForty-three patients with DENV infection were enrolled. Mean patient age was 75.0 ± 12.2 years and the case fatality rate was 44.2% (19/43). Significantly more non-survivors than survivors had increased ST2 level (78.9% vs. 12.5%, p < 0.001). The AUC value for serum ΔsST2 level was 0.857 for predicting DENV fatality. Moreover, patients given frozen fresh plasma (FFP) transfusions were significantly (p = 0.025) more likely to have higher serum ST2 level changes than were those who had not. DENV-infected patients with early bloodstream infections (BSIs) seemed to have higher ST2 levels than those who did not have BSIs.ConclusionsSerum ST2 levels increased in the elderly (≥ 65 years of age) with DENV infection. The changes in serum sST2 levels might be a critical indicator of DENV infection severity for the elderly; sST2 is an important modulator of coagulopathy in severe DENV infections.
| S-EPMC6948823 | biostudies-literature
Project description:Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS). Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques. Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = -0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups. Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04797819.
| S-EPMC8341076 | biostudies-literature
Project description:ObjectiveST2 is a member of the toll-like receptor superfamily that can alter inflammatory signaling of helper T-cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.MethodsWe measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0-2 and 3-6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan-Meier survival analysis and receiver operating characteristic curves.Results646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2-12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7-49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9-55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54-5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58-8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40-37.44, P = 0.039).InterpretationSoluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.
| S-EPMC5553222 | biostudies-literature