Serum Galectin-3 Research Articles

Relationships between the activity of neurohormonal systems and intracardiac hemodynamics in patients with heart failure: focus on galectin-3

The introduction of novel biomarkers necessitates their detailed study in patients with different heart failure (HF) phenotypes as part of a personalized approach to assessing the disease severity and predicting outcomes.Aim. To assessthe activity of following neurohormonal systems: N-terminal probrain natriuretic peptide (NT-proBNP) and galectin-3 in HF with preserved, mildly reduced and reduced ejection fraction (EF).Material and methods. In 69 patients with NYHA class II-IV HF, along with a general clinical examination, the level of NT-proBNP and serum galectin-3 was determined by enzyme immunoassay.Results. Patients included in the study were divided into 3 groups: preserved EF (HFpEF) — 23 patients, mildly reduced EF (HFmrEF) — 26 patients, and reduced EF (HFrEF) — 20 patients. In patients with HF, the level of galectin-3 did not directly depend on EF, but was associated with NT-proBNP level as follows: there was a tendency to increase the concentration of galectin-3 in the tertile groups of NT-proBNP. Correlation analysis revealed significant feedback (r=-0,41, p<0,05) between galectin-3 and left ventricular EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum values of serum galectin-3 indices were noted, reaching 10,5 [6,5; 14,5] ng/ml.Conclusion. Analysis of neurohormonal activity demonstrated a unidirectional increase in NT-proBNP and galectin-3 in patients with HF, regardless of left ventricular EF, while the maximum values of galetin-3 were observed in patients with HFpEF.

Proposal of a prediction model for prognosis of patients with acute myocardial infarction after percutaneous coronary intervention based on galectin-3 and soluble growth stimulating expressed gene 2 levels

Abstract Background: To study the correlations of serum galectin-3 (Gal-3) and soluble growth stimulating expressed gene 2 (sST2) levels with prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Methods: A total of 112 patients diagnosed from August 2015 to October 2017 were selected. They were followed up for 3 years. Based on major adverse cardiovascular events (MACEs) during follow-up, they were divided into MACE and non-MACE groups. Multivariate logistic regression analysis was performed to explore the independent risk factors for MACEs. A nomogram model was established using the factors and validated. The optimal cut-off values of Gal-3 and sST2 levels were determined by receiver operating characteristic curves. Kaplan-Meier method was used for survival analysis. Results: MACEs occurred in 78 patients during follow-up. Patients in the MACE group were more often hypertensive, had higher total cholesterol, uric acid, sST2 and Gal-3, and lower left ventricular ejection fraction (LVEF) (P<0.05). CK-MB, sST2, Gal-3 and LVEF were the independent risk factors for MACEs (P<0.05). The nomogram model established with these factors had high accuracy for predicting overall survival, and its concordance index (C-index) was 0.768 (95% confidence interval: 0.692-0.865). The prognosis of the patients with Gal-3 ≥12.57 μg/ mL and sST2 ≥18.56 ng/mL was poorer 3 years after PCI. Conclusions: The levels of serum Gal-3 and sST2 are the independent risk factors for MACEs in AMI patients following PCI, with high prognostic value.

CLINICAL VALUE OF GALECTIN-3 IN DIFFERENTIATING PAPILLARY THYROID CANCER FROM NODULAR GOITER

"Introduction: Thyroid cancer in one of the most common cancers worldwide, with an increasing incidence over the last decades. Serum Galectin-3 (Gal-3) is used as biomarker in different types of cancer (gastric, hepatic), but its utility in papillary thyroid cancer differential diagnostic in still inconclusive. Objectives: The present study aims to evaluate the diagnostic value of preoperative serum Galectin-3 levels in differentiating between papillary thyroid cancer and nodular goiter. Methods: 277 of serum samples from patients with thyroid lesions were divided into two subgroups: nodular goiter (NG; n = 121) and papillary thyroid carcinoma (PTC; n = 136). Serum Gal-3 levels were measured before surgery for the entire group, and for 62 patients (33 NG, 29 PTC) it was measured a month post-surgery. Gal-3 was measured by ELISA, using Human Galectin-3 Quantikinine ELISA kit (R&D Systems) and statistical analysis were performed using MedCalc Software. All paticipants signed the written informed consent and the study was approved by the Ethics Commitee of the C.I. Parhon National Institute of Endocrinology, Bucharest. Results: Circulating Gal-3 values show that this biomarker has a higher value in PTC patients compared with NG patients (7.17 ng/ml vs. 8.285 ng/ml, p = 0.0038), before thyroidectomy. There were not observed significant statistical correlations between serum Gal-3 values and histological subtype, focality, invasivity or dominant nodule dimension. Conclusion: Our results regarding Gal-3 values show that this biomarker has a higher value in PTC patients compared with NG patients, but its clinical value in preoperative diagnosis and evaluation of thyroid nodules needs further investigations. Keywords: thyroid cancer, papillary thyroid carcinoma, galectin-3"

Serum galectin-3 and aldosterone: potential biomarkers of cardiac complications in patients with COVID-19.

Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV-2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in-vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19.

Can galectin-3 be used to predict the severity of vasoocclusive crisis in patients with sickle cell anaemia?

Objective: The number of markers showing the severity of the disease and the number of drugs that can be used in the treatment is very low in vasooclusive crises seen in patients with sickle cell anemia. This study aims to evaluate the levels and changes of serum galectin-3 levels, which are known to have many roles in the body, during a painful crisis. Material and Methods: In addition to the 0th and 48th hour galectin-3 levels in patients hospitalized for a painful crisis, galectin-3 measurements were also performed in stable patients with sickle cell anemia and healthy individuals. Results: Galectin-3 levels were statistically significantly different in patient groups (p=0.001). It was observed that galectin-3 levels at the 48th hour were markedly higher than at the 0th hour in patients with painful crises. It was found that galectin-3 levels at both 0th and 48th hours were correlated with the duration of hospitalization due to painful crisis and the period of intravenous opioid use. Conclusion: Galectin-3 levels, which are elevated during the painful crisis in patients with sickle cell anemia, are associated with the severity of the painful crisis

Association Between Serum Galectin-3 Levels and Coronary Stenosis Severity in Patients With Coronary Artery Disease.

BackgroundThe relationship between galectin-3 (Gal-3) and coronary artery disease (CAD) has not been fully elucidated.AimThis study aimed to determine the relationship between the presence and severity of CAD and serum Gal-3 levels.Patients and MethodsThree-hundred thirty-one consecutive CAD patients were enrolled as the study group. An additional 62 patients without CAD were enrolled as the control group. Serum Gal-3 levels were separately compared between the non-CAD and CAD groups, among the stable CAD and Acute coronary syndrome (ACS) groups, and between CAD patients with low and high SYNTAX scores (SSs). The 1-year cumulative rate of major adverse cardiac events (MACEs) was also compared among ACS patients by Gal-3 levels.ResultsSerum Gal-3 was significantly higher in the CAD group than in the non-CAD group 3.89 (0.16–63.67) vs. 2.07 (0.23–9.38) ng/ml, P < 0.001. Furthermore, serum Gal-3 was significantly higher in the non-ST-segment elevation ACS (NSTE-ACS) group than that in the stable CAD group, 4.72 (1.0–16.14) vs. 2.23 (0.65–23.8) ng/ml, P = 0.04 and higher in the ST-segment elevation myocardial infarction (STEMI) group than that in the stable CAD group 7.87 (0.59–63.67) vs. 2.23 (0.65–23.8) ng/ml, P < 0.001. Serum Gal-3 level was an independent predictor of ACS compared with stable CAD group (OR = 1.131, 95% CI: 1.051–1.217, P = 0.001) as well as high SS (OR = 1.030, 95% CI: 1.021–1.047, P = 0.038) after adjust other confounding risk factors. Acute coronary syndrome patients with Gal-3 levels above the median (gal-3 = 4.78 ng/ml) showed a higher cumulative MACE rate than those with Gal-3 levels below the median. After adjusting other confounding risk factors, Gal-3 remained an independent risk factor for the cumulative rate of MACEs in ACS patients (6% higher rate of MACEs incidence per 1 ng/ml increment of Gal-3).ConclusionGalectin-3 correlated with the presence of CAD as well as coronary stability and complexity. Galectin-3 may be valuable in predicting mid-term prognosis in ACS patients.

Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47–9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79–0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

Diagnostic Value of Serum Concentration of Galectin-3 in Patients With Heart Failure With Preserved Ejection Fraction.

BackgroundAlthough the predictive value of galectin-3 for heart failure with preserved ejection fraction has been demonstrated, the diagnostic value remains unclear. The present study was performed to address this issue.HypothesisGalectin-3 has diagnostic value for heart failure with preserved ejection fraction.MethodsThis is a diagnostic experiment. We conducted an observational study of 223 patients with combined symptoms of heart failure and diseases that can lead to heart failure with preserved ejection fraction. Patients were grouped into the heart failure group and control group in accordance with the 2016 European Society of Cardiology heart failure guidelines for heart failure with preserved ejection fraction. Baseline information and serum galectin-3 concentration were assessed within 24 h after admission.ResultsSerum galectin-3 concentration was significantly higher in the heart failure group compared with the control group. Binary logistic regression analysis showed that higher galectin-3 concentration was associated with the occurrence of heart failure with preserved ejection fraction. The area under the curve of galectin-3 was 0.763, indicating that galectin-3 has moderate diagnostic value for heart failure with preserved ejection fraction. Galectin-3 >15.974 ng/mL identified heart failure with preserved ejection fraction with 76.0% sensitivity and 71.9% specificity.ConclusionsThere was a correlation between galectin-3 and heart failure with preserved ejection fraction, and galectin-3 was an independent predictor of heart failure with preserved ejection fraction. The diagnostic value of galectin-3 for heart failure with preserved ejection fraction was moderate (AUC: 0.763, 95% CI: 0.696–0.821, P < 0.01, and the sensitivity is 76.0% while the specificity is 71.9% at the threshold 15.974 ng/mL) and was higher than that of interventricular septal thickness or E/A ratio.

Therapeutic implications of galectin-3 in patients with atrial fibrillation

Atrial fibrosis can present as an arrhythmogenic substrate that is correlated with higher recurrence after catheter ablation for atrial fibrillation. Galectin-3, a beta-galactoside-binding lectin, is highly expressed and secreted from macrophages and is important in inflammation and fibrosis. We assessed the clinical implications of serum galectin-3 in patients with atrial fibrillation. This was a prospective cohort study of consecutive patients who underwent radiofrequency catheter ablation in a tertiary referral center from February 2017 to September 2017. Intracardiac blood sampling, echocardiographic measurements, magnetic resonance imaging with late gadolinium enhancement, electrophysiologic testing, and endocardial voltage mapping were consistently implemented in 75 patients before the ablation. Serum galectin-3 level was higher in patients with diabetes mellitus and was correlated with values that indicated the left atrial size. During a median 14 months of follow-up, atrial tachyarrhythmia recurred in 27% of patients. In multivariable Cox regression analysis, non-paroxysmal atrial fibrillation (hazard ratio 6.8; 95% confidence interval 1.6–28.9) and higher galectin-3 levels (hazard ratio 1.3; 95% confidence interval 1.0–1.7) were associated with increased risk of recurrence. Serum galectin-3 may be a prognostic biomarker for risk stratification in patients with atrial fibrillation planned catheter ablation.

Establishment of Galectin-3 Time-resolved Fluoroimmunoassay and its Application in Idiopathic Membranous Nephropathy.

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression.The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN.The sensitivity of the Gal-3-TRFIA assay was 0.85ng/mL, and the detection range was 0.85-1000ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90ng/mL) compared to healthy controls (16.29 ± 9.91ng/mL, P < 0.0001).In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.

Galectin-3 as a Novel Multifaceted and Not Only Cardiovascular Biomarker in Patients with Psoriasis with Regard to Systemic Treatment-Preliminary Data.

Simple SummaryGalectin-3 (gal-3) regulates many different biological processes and diseases, which are common accompanying diseases of psoriasis. Psoriasis is one of the most common skin diseases. There is little information about potential diagnostic role of gal-3 in psoriasis. Serum gal-3 concentrations were measured before and after twelve weeks of antipsoriatic treatment in patients with psoriasis and compared to 11 persons without psoriasis (control group). Serum gal-3 level in patients with psoriasis was significantly higher compared to the control group. In obese patients and long-lasting psoriasis positive relations of gal-3 and index of psoriasis severity were noted. In psoriatics with low gal-3 levels, it was noted that the higher the gal-3, the higher the BMI and glucose level. In patients with long history of psoriasis it was observed that the higher gal-3, the lower the lipids levels. The Gal-3 level might be a factor affecting the course of psoriasis and useful in prediction of cardiometabolic comorbidities, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and a short history of psoriasis may have greater risk of diabetes. In obese patients with long-lasting psoriasis, gal-3 may have a beneficial influence against abnormal lipid profiles or perhaps further cardiovascular disorder development.Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group. The mean serum galectin-3 level in patients with psoriasis was significantly higher compared to the control group (p < 0.01). In patients with obesity and long-lasting psoriasis (>20 years) positive relations of gal-3 and PASI were noted. In psoriatics with low gal-3 levels, positive correlations between the gal-3 and BMI, glucose level, and with the latter in short-lasting psoriasis (<20 years) were noted. In the long history of psoriasis, gal-3 was negatively correlated with lipids levels. The Gal-3 level might be a multifaceted modulator of the course of psoriasis and predictive factor of cardiometabolic comorbidities’ development, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and short history of psoriasis are presumably at greater risk of diabetes. In patients with long-lasting psoriasis and concomitant obesity, gal-3 may exert a protective role against dyslipidemia or perhaps further CMD development.

Serum Galectin-3 levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study

BackgroundHigher serum galectin-3 levels are related to adverse outcomes in different disease states. However, the association of galectin-3 with mortality in the maintenance hemodialysis (HD) population has not been fully described. Thus, we aimed to assess the predictive significance of galectin-3 for all-cause and cardiovascular (CV) mortality through a Chinese maintenance HD population.MethodsA prospective cohort study was conducted in five hundred and six patients with end-stage renal disease who underwent hemodialysis at Dalian Central Hospital before December 31, 2014. Serum galectin-3 levels were measured at baseline and classified as high (> 8.65 ng/ml) or low (≤ 8.65 ng/ml) according to the “X-tile” program. Primary and secondary outcomes were all-cause and CV mortality, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards regression models.ResultsDuring the median follow-up of 60 months, there were 188 all-cause deaths and 125 CV deaths. Compared with maintenance HD population with galectin-3 ≤ 8.65 ng/ml, the adjusted HR for all-cause mortality among those with galectin-3 > 8.65 ng/ml was 1.59 (CI: 0.96–2.65, p = 0.07). Furthermore, multivariable analysis showed that maintenance HD patients with galectin-3 > 8.65 ng/ml had a 2.13-fold higher risk of CV death than those with galectin-3 ≤ 8.65 ng/ml (HR = 2.13, 95% CI 1.07–4.26).ConclusionGalectin-3 is an independent predictor of CV mortality in maintenance HD patients.

Galectin-3 as a Novel Biomarker for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Galectin-3 has been shown to play a key pathophysiological role in pulmonary associated inflammatory response and lung fibrosis in COVID-19 and is a mediator for viral adhesion. However, there is limited data about its potential role in severity and prognosis of COVID-19. This study aimed to investigate the predictive role of serum galectin-3 concentrations in the severe clinical outcomes of hospitalized COVID-19 patients: the severity of pneumonia, in-hospital mortality, and the need for intensive care unit (ICU) admission. This single-center study included 68 patients with laboratory- and radiologically-confirmed COVID-19 admitted to our emergency department. The study population was divided into patients with primary clinical out-comes (n = 32) and those without (n = 36). The need for ICU admission and/or in-hospital mortality were the primary clinical endpoints. The study group was also classified based on pneumonia severity: severe or mild/moderate. Blood samples were collected within 48 hours of admission to estimate serum galectin-3 concentrations. Multivariate regression analysis showed that lower concentrations of galectin-3 and arterial oxygen saturation (SpO2) were independently associated with the primary clinical outcomes (OR = 0.951, p = 0.035; OR = 0.862, p = 0.017, respectively); increased concentrations of galectin-3 were an independent predictor of severe pneumonia (OR = 1.087, p = 0.016). In the receiver operating characteristics curve analysis, serum galectin-3 concentrations at hospital admission predicted pneumonia severity with 52.1% sensitivity and 90% specificity with a cutoff of 38.76 ng/mL. Circulating galectin-3 at hospital admission could be a useful biomarker for identifying COVID-19 patients at high risk for severe pneumonia.

Modification of Serum Galectin-3 and Reversal of Cardiac Remodeling Following Pediatric Transcatheter Atrial Septal Defect Closure

Objectives: We aimed to evaluate the effect of percutaneous atrial septal defect (ASD) closure in children using right heart indices and serum galectin-3 (Gal-3), as potential biomarkers of right heart remodeling. Methods: This case–control prospective study included 40 children with ASD and 25 control subjects. An echocardiographic evaluation was performed before the procedure, as well as 24 h, 1 month, and 6 months after intervention. Serum Gal-3 was measured before, and 1 month after the procedure. Results: Serum Gal-3 concentration, right atrial (RA) dimensions, right ventricular (RV) dimensions, indexed RA area, and right index of myocardial performance (RIMP) were significantly increased in children with ASD compared with control subjects while tricuspid annular plane systolic excursion (TAPSE) was significantly decreased. Six months after closure, RA, and RV dimensions significantly decreased and RV function improved (RIMP decreased and TAPSE increased). Gal-3 oncentration significantly decreased 1 month after ASD closure, but it did not reach normal range compared with control subjects. A positive correlation between Gal-3 and age at closure, RA area, RV dimensions, and RIMP was observed. A positive correlation was observed between the decrease in Gal-3 concentration and the decrease in RA area and RV dimensions 1 month after ASD closure. A significant negative correlation was observed between TAPSE and Gal-3 concentration before and after intervention. Conclusions: Percutaneous ASD closure can improve right-sided indices and decrease serum Gal-3 concentration. Gal-3 can be used as a sensitive biomarker of right heart remodeling, with a decrease in Gal-3 concentration suggesting reversal of maladaptive remodeling.

Galectin-3 as a prognostic biomarker for diabetic nephropathy

Background Diabetes mellitus (DM) type 2 is a major health condition that has shown an increased incidence globally. The most common complication in type 2 DM is diabetic nephropathy (DN). Aim To determine serum galectin-3 as a prognostic biomarker in type 2 DN. Patients and methods A case–control prospective study was done in the Internal Medicine Department of AL-Zahraa University Hospital, Cairo, Egypt. The study was conducted on 90 patients, including 60 patients with type 2 DM and 30 age-matched and sex-matched healthy volunteers as a control group. The 90 patients were classified into four groups: group I included 20 diabetic patients (type 2) with an albumin/creatinine ratio (ACR) of less than 30 mg/g (normoalbuminuria), group II included 20 DM (type 2) with an ACR of 30–300 mg/g (microalbuminuria), group III included 20 DM (type 2) with an ACR of more than 300 mg/g (macroalbuminuria), and control group included 30 age-matched and sex-matched healthy individuals. History, examination, fasting blood sugar, glycated hemoglobin, urea, creatinine, estimated glomerular filtration rate, ACR, lipid profile, and serum galectin-3 were done for all participants. The study was approved by the Al Azhar University Ethics Board. Results Galectin-3 was significantly higher in patients with macroalbuminuria than in those with microalbuminuria and normoalbuminuria. Galectin-3 level has a significant positive correlation with parameters of DN progression (age, DM duration, fasting blood sugar, glycated hemoglobin, cholesterol, low-density lipoprotein, triglyceride, urea, creatinine, and ACR) and a significant negative correlation with estimated glomerular filtration rate and high-density lipoprotein levels. Conclusion Galectin-3 was significantly higher in type 2 diabetic patients with macroalbuminuria than in those with microalbuminuria and normoalbuminuria.

Galectin-3 as a Potential Biomarker of Microvascular Complications in Patients with Type 2 Diabetes.

Human Galectin-3 is a 32- to 35-kDa size lectin, mainly comprises a C-terminal carbohydrate recognition binding domain (CRD) and N-terminal domain. It acts as a powerful pro-inflammatory signalling factor, which plays an important role in the activation, chemotaxis, and cytokine release of inflammatory cells. Galectin-3 has also been studied in relation to development of insulin resistance. The levels of galectin-3 have been observed to be associated with both diabetes prevalence and incidence, independent of traditional diabetes risk factors. It is also associated with development of microvascular complications of diabetes mellitus like retinopathy, nephropathy and neuropathy. Tertiary care hospital-based cross-sectional prospective study. 150 patients selected by simple random sampling and were divided into 3 groups., Group A - Patients of Type 2 Diabetes mellitus without microvascular complications (n=50), Group B - patients of Type 2 diabetes mellitus with microvascular complications (n=50) and Group C - Healthy control (n=50). Descriptive statistics was performed by calculating mean and standard deviation for the continuous variables. chi-square goodness-to-fit test, Student T test (unpaired) and Analysis of variance (ANOVA) and multivariate analysis were used to compare means. The p-value was taken significant when less than 0.05 (P<0.05) and a confidence interval of 95%. In group A, B and C majority of patients were between 56-60 years with 34%, 40% and 36% cases, respectively. The mean BMI shows that the Patients with complications had significantly higher BMI than those without complications and controls had significantly lower BMI than patients having diabetes. The data shows statistical significance with deranged biochemical profile in patients with DM with complications as compared to patients without complications and control group. In both groups A and B patients with HbA1c between 9.1-12 had mean serum galectin level (20.2 in group A, 25.9 in group B) significantly higher than patients with HbA1c between 6.5-9 (18.5 in group A and 20.4 in group B). patients with deranged lipid profile had significantly higher serum galectin level in all 3 groups, with cases from group B having higher values than group A. While controls had the lowest value of serum galectin (P value<0.001). There was a highly significant correlation between high serum galectin levels and the incidence of both non-progressive and progressive retinopathy (P value=0.0001). The mean galectin of patients with neuropathy was 28.3 ± 3.1 ng/ml, which was significantly higher than patients from group B without neuropathy (24.5 ± 2.6 ng/ml). The mean serum galectin level of patients with macroalbuminuria was 30.1± 1.3 ng/ml which was significantly higher than those with microalbuminuria having mean galectin level of 22.8 ±4.8 ng/ml. There was a highly significant correlation between high serum galectin levels and the incidence of both micro and macroalbuminuria (P value=0.0001). This study concludes that elevated serum Galectin-3 levels are associated with diabetes-related chronic inflammatory processing pathway, and closely relates to the severity of diabetes in T2DM both with and without complications. Therefore, Galectin-3 may be helpful in the diagnosis and prognosis of microvascular and macrovascular complications in T2DM patients.

Assessment of serum galectin-3 levels in acute rheumatic fever

Galectin-3 is a biomarker which takes a role in both acute and chronic inflammation as well as fibrosis and oxidative stress. Increased levels of it are associated with cardiovascular diseases. This study was performed to investigate the levels of galectin-3 in acute rheumatic fever (ARF). 30 patients with ARF and 26 healthy children were included. Galectin-3 levels of the patients were compared with the controls, as well as within the patients before and after the treatment. The patients had significantly lower galectin-3 levels on admission than the control (p=0.02), but its levels were not significantly different between these groups at the end of treatment (p=0.714). The mean galectin-3 levels of the patients were increased after the treatment (p < 0.001). Severity of carditis and galectin-3 levels were negatively correlated (r=-539, p=0.02). Children with ARF have significantly reduced levels of galectin-3 and there is a negative correlation between the severity of the carditis and galectin-3 levels. Studies with larger sample sizes may give more accurate data about the role of galectin-3 in ARF.

The Role of Serum Galectin-3 Levels in Patients with Sarcoidosis

Introduction: Galectin-3 is a multifunctional protein, the levels of which increase in the presence of diseases that progress with pulmonary fibrosis. This study investigated the role of galectin-3 levels in the staging and assessing of the severity of sarcoidosis. Methods and Subjects: Seventy-three subjects were studied; 25 were healthy individuals and 48 patients had pathologically confirmed diagnosis of sarcoidosis in which other potential causes had been ruled out. Galectin-3 levels were measured and compared in terms of such parameters as hemogram, biochemistry, age, body mass index, and smoking status. Results: The mean galectin-3 levels of the sarcoidosis patients (14.87 ± 5.57) were significantly higher than those in the healthy subjects (11.81 ± 2.67), and the mean galectin-3 levels differed significantly among different stages of the disease (p < 0.05). The serum galectin-3 level in patients with stage 2, 3, and 4 sarcoidosis was found to be higher than in patients with stage 0 and 1 sarcoidosis and the control group. In addition, serum galectin-3 levels in the sarcoidosis patients had significant positive correlations with blood urea nitrogen, alkaline phosphatase, white blood cells, red blood cell, hemoglobin, and neutrophil levels (34.9% [p < 0.05]; 40.1% [p < 0.05]; 41.2% [p < 0.01]; 43.3% [p < 0.01]; 34.7% [p < 0.05]; and 40.6% [p < 0.01], respectively) and a significant negative correlation with the platelet distribution width levels (p < 0.05). Conclusion: Serum galectin-3 levels are significantly elevated in sarcoidosis patients with parenchymal involvement at stage 2 or higher, suggesting that serum galectin-3 levels can be used to estimate disease severity in sarcoidosis.

Myocardial Involvement Detected Using Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis: A Prospective Observational Study.

Introduction and objectives: Cardiac involvement in systemic sclerosis (SSc) patients affects mortality. Cardiac magnetic resonance (CMR) is capable of detecting structural changes, including diffuse myocardial fibrosis that may develop over time. Our aim was to evaluate myocardial structure and function changes using CMR in patients with SSc without known cardiac disease during a 5-year follow-up and find possible correlations with selected biomarkers. Methods: A total of 25 patients underwent baseline and follow-up CMR examinations according to a pre-specified protocol. Standard biochemistry, five biomarkers (hsTnI, NT-proBNP, galectin-3, sST2, and GDF-15), and disease-specific functional parameters enabling the classification of disease severity were also measured. Results: After five years, no patient suffered from manifest heart disease. Mean extracellular volume (ECV) and T1 mapping values did not change significantly (p ≥ 0.073). However, individual increases in native T1 time and ECV correlated with increased galectin-3 serum levels (r = 0.56; p = 0.0050, and r = 0.71; p = 0.0001, respectively). The progression of skin involvement assessed using the Rodnan skin score and a decrease in the diffusing capacity of the lungs were associated with increased GDF-15 values (r = 0.63; p = 0.0009, and r = −0.51; p = 0.011, respectively). Conclusions: During the 5-year follow-up, there was no new onset of heart disease observed in patients with SSc. However, in some patients, CMR detected progression of sub-clinical myocardial fibrosis that significantly correlated with elevated galectin-3 levels. GDF-15 values were found to be associated with disease severity progression.

Abstract 12459: Downregulated Fli1 in Scleroderma Myeloid Cells May Contribute to Cardiac Fibrosis via a Galectin-3/mTOR Dependent Pathway

Introduction: Scleroderma (SSc) is an autoimmune fibrotic disease with high mortality and no effective therapies. Cardiac fibrosis in SSc is common and has a poor prognosis, but pathogenesis is unclear. Galectin-3 secretion by macrophages has been implicated in cardiac fibrosis, but its specific contribution to SSc cardiac disease has not been elucidated. We recently demonstrated that Fli1, a member of the Ets family of transcription factors, is decreased in SSc myeloid cells, and that Fli1 depleted macrophages have a profibrotic phenotype. We aim to evaluate the contribution of myeloid Fli1 to SSc cardiac fibrosis. Methods: Levels of galectin-3 were assessed by ELISA in serum, and qPCR and immunofluorescence in monocytes. Primary human cardiac fibroblasts were co-cultured with macrophages using inserts. Rapamycin (10nM) was used to treat the co-cultures. Western blot was used to assess protein levels of collagen and p70S6K. Collagen deposition in hearts from mice with conditional deletion of Fli1 in macrophages ( LysMCre/Fli1 fl/f l ) was assessed by picrosirius red. Results: SSc patients had higher expression of galectin-3 in monocytes and serum compared to healthy controls. Co-culture of human cardiac fibroblasts and Fli1 depleted macrophages resulted in induction of galectin-3 expression by macrophages, and activation of the mTOR/p70S6K pathway with enhanced collagen type I protein deposition by fibroblasts. These effects were blocked by the mTOR inhibitor Rapamycin, and by treatment of macrophages with siRNA against galectin-3. Deletion of Fli1 in macrophages via Cre-mediated recombination using LysMCre mice predisposed mice to develop cardiac fibrosis. Conclusions: These findings suggest that Fli1 deficiency in macrophages may contribute to SSc cardiac fibrosis, and that Rapamycin may be a potential therapeutic option for heart involvement in SSc.