Plasma Galectin-3 Research Articles

THE ROLE OF NEUROHORMONAL FACTORS IN THE FORMATION OF A PATIENT’S CLINICAL PROFILE AND THE IMPACT ON STRUCTURAL CARDIAC AND VASCULAR REMODELING IN PATIENTS WITH MYOCARDIAL INFARCTION AFTER REPERFUSION THERAPY

The aim: To determine the dynamics of galectin-3 in the formation of the patient’s clinical profile and the impact on structural cardiac and vascular remodeling in patients with myocardial infarction after reperfusion therapy. Materials and methods: 140 patients with class II A CHF syndrome according to Vasilenko-Strazhesko FC II-III (NYHA), which occurred in patients with MI, and 22 patients with MI without signs of CHF were examined. Results: The average serum galectin-3 level of the studied patients was analyzed. The average concentration of galectin-3 in patients with stenting without signs of CHF was (10.87±1.65) ng/ml comparing to (6.57±0.21) ng/ml in healthy subjects (p<0.05). An increase in the concentration of this indicator was observed in the group of patients with CHF after MI with reperfusion - (35.2±1.76) ng/ml, which is significantly higher in comparison with practically healthy subjects, and in patients without revascularization it was (38.94±1.97) ng/ml (p<0.001). Positive correlations of medium strength were found between left ventricular end-systolic volume (ESV), left ventricular end-diastolic volume (LVEDV) and serum galectin-3 concentration in the examined patients. The correlation coefficient between the abovementioned indicators was 0.60 (p<0.01) and 0.53 (p<0.05), respectively. Conclusions: It has been determined that in patients with CHF with postinfarction cardiosclerosis there is a direct correlation of medium strength between the values of indicators of LV myocardial remodeling with plasma galectin-3 concentration, including ESV, EDV, in examined patients. The role of galectin-3 as a marker of postinfarction remodeling in patients with CHF for early diagnosis, prognosis, and risk stratification has been presented.

Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event.

Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05-0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3-59.4] ng/mL vs. 18.9 [14.5-23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.

Plasma levels of galectin-3 in residents of the Podillya region of Ukraine without signs of cardiovascular pathology carriers of different variants of the coding gene (LGALS-3, rs 2274273)

Annotation. The purpose of the study is to investigate the plasma level of galectin-3 in postmenopausal women without signs of cardiovascular pathology and its possible association with the structural and functional parameters of the myocardium in carriers of different polymorphic variants of the coding gene (LGALS-3, rs2274273). 67 women of postmenopausal age (average age 56.43±0.64 years) without signs of cardiovascular pathology residents of the Podillya region of Ukraine were examined. In addition to the general clinical examination, the research used the enzyme immunoassay method to determine the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene at the rs2274273 locus by means of polymerase chain reaction, and ultrasound of the heart. Statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. By means of correlation analysis with the calculation of Spearman's rank correlation coefficients (r), an assessment of the possible association of the plasma level of the biomarker and the structural and functional indicators of the heart was carried out. The critical value of the significance level (p) was ≤0.05. In the examined population of women, there was no significant difference between the frequency of occurrence of the GA and GG genotypes carriers of the galectin-3 gene locus rs2274273: 49.25% (n=33) and 40.30% (n=27), respectively (p>0.05). The AA genotype variant was found in 10.45% (n=7) of individuals, which is significantly less frequent than both the GA and GG genotypes (p<0.01). The frequency of distribution of genotypes corresponded to the Hardy-Weinberg equilibrium. The average level of galletin-3 in blood plasma in women was 6.68±0.30 ng/ml, it was within the generally accepted norms and did not reliably differ from the corresponding indicators in men of the same region. No significant difference in plasma concentrations of galectin-3 was found in carriers of different polymorphic variants of the galectin-3 gene. Correlation between the level of galectin-3 in the blood plasma and most indicators of intracardiac and systemic hemodynamics in women without cardiovascular pathology was not found. In the future, it is planned to study the formation of prerequisites for chronic heart failure (CHF) in women with EH based on indicators of the plasma level of galectin-3 in carriers of polymorphic variants of the coding gene (LGALS-3, rs2274273).

The plasma galectin-3 level has high specificity and sensitivity for predicting postoperative atrial fibrillation after coronary artery bypass surgery.

Postoperative new-onset atrial fibrillation (POAF) commonly occurs after coronary artery bypass graft (CABG) surgery. This study aimed to determine the utility of the preoperative netrin-1 and galectin-3 levels for predicting POAF following CABG surgery, as well as that of postoperative serial measurement for assessing these markers' patterns of expression. This prospective cohort study included 50 patients that underwent CABG surgery. The plasma netrin-1 and galectin-3 levels were measured via enzyme-linked immunosorbent assay (ELISA) before surgery (baseline) and at 6, 12, and 24 h after surgery. The patients were divided into two groups according to the occurrence of POAF; the POAF (+) group and the POAF (-) group. In total, 26 patients developed POAF, whereas 24 remained in sinus rhythm. Baseline galectin-3 levels were higher in the POAF (+) group than in the POAF (-) group (30.7 ± 10.1 pg mL-1 and 15.7 ± 3.6 pg mL-1, respectively). The post-CABG surgery galectin-3 level increased in both the POAF (+) and POAF (-) groups at 6 h (46.2 ± 26.3 pg mL-1 and 24.9 ± 5.9 pg mL-1, respectively), 12 h (45.2 ± 24.1 pg mL-1 and 26.6 ± 9.3 pg mL-1, respectively), and 24 h (54.2 ± 33.5 pg mL-1and 28.6 ± 7.7 pg mL-1, respectively). The plasma netrin-1 level did not differ between groups at baseline or at 6, 12, and 24 h post CABG surgery. Whereas netrin-1 does not appear to have any utility as a marker for the development of POAF in CABG surgery patients, the plasma galectin-3 level has high specificity and sensitivity for predicting POAF following CABG surgery and could be considered a marker for predicting POAF.

Placental galectin-3 is reduced in early-onset preeclampsia.

Preeclampsia is a disease of pregnancy responsible for significant maternal and neonatal mortality. Galectin-3 is a β-Galactoside binding protein. This study aimed to characterise galectin-3 in women with preeclampsia and human trophoblast stem cells (hTSCs). Galectin-3 was measured in placental lysates and plasma collected from patients with early-onset preeclampsia (delivered <34 weeks’ gestation) and gestation matched controls. Placental galectin-3 protein was significantly reduced in 43 women with early-onset preeclampsia compared to 21 controls. mRNA expression of LGALS3 (galectin-3 encoding gene) was reduced in 29 women with early-onset preeclampsia, compared to 18 controls (p = 0.009). There was no significant difference in plasma galectin-3 protein in 46 women with early-onset preeclampsia compared to 20 controls. In a separate cohort of samples collected at 36 weeks’ gestation, circulating galectin-3 was not altered in 23 women who later developed preeclampsia, versus 182 who did not. In syncytialised hTSCs, hypoxia increased mRNA expression of LGALS3 (p = 0.01). Treatment with inflammatory cytokines (TNF-α and IL-6) had no effect on LGALS3 mRNA expression. However, TNF-α treatment caused an increase in mRNA expression of LGALS3BP (galectin-3 binding protein encoding gene) in hTSCs (p = 0.03). This study showed a reduction of galectin-3 in placenta from pregnancies complicated by early-onset preeclampsia. LGALS3 mRNA expression was dysregulated by hypoxia exposure in placental stem cells.

Measurement of Plasma Galectin-3 Concentrations in Patients with Catheter Infections: A Post Hoc Retrospective Cohort Study.

Catheter-related infections (CRIs) include catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), and they are associated with high morbidity, mortality, and healthcare costs. The diagnosis of a CRI is made difficult by its non-specific symptoms. We aimed to investigate the factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for CRIs. Circulating the concentrations of galectin-3, we measured the chemokine (C-C) motif ligand 2, procalcitonin, and C-reactive protein in 110 patients with a central catheter, in 165 patients with a urinary catheter, and in 72 control subjects. Catheter-bearing patients had higher concentrations (p < 0.001) of galectin-3 than the control group [central catheter: 19.1 (14.0–23.4) µg/L; urinary catheter: 17.1 (12.7–25.4) µg/L; control group: 6.1 (5.0–8.7) µg/L]. We identified chronic kidney disease as an independent determinant of galectin-3 concentrations in patients with a central catheter, and serum creatinine, cardiovascular disease, and number of days that the catheter was indwelling were identified as determinants in urinary catheter patients. We found that measuring galectin-3 concentrations in urinary catheter patients with a CRI was more accurate for diagnosis than the other parameters. We conclude that the measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of CRIs in those with a urinary catheter.

Plasma galectin-3 concentration and estimated glomerular filtration rate in patients with type 2 diabetes with and without albuminuria

This study aimed to investigate the association between galectin-3 concentration and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria. In this cross-sectional study, we examined 334 patients with T2DM. The eGFR was calculated using a creatinine-based formula (eGFRcrea) and a combined creatinine-cystatin C equation (eGFRcrea-cyst). The participants were categorized into two groups based on the urinary albumin-to-creatinine ratio (UACR): patients without albuminuria (UACR < 30 mg/g) and those with albuminuria (UACR ≥ 30 mg/g). Greater concentrations of plasma galectin-3 were associated with lower eGFRcrea-cyst and eGFRcrea levels in patients with and without albuminuria. Plasma galectin-3 concentrations were negatively correlated with eGFRcrea-cyst in patients with normoalbuminuria and albuminuria (γ = − 0.405, P < 0.001; γ = − 0.525, P < 0.001, respectively). Galectin-3 concentrations were significantly associated with eGFRcrea-cyst after adjusting for sex, age, and other confounding factors, including UACR as a categorical or continuous variable in multiple regression analyses (β = − 0.294, 95% CI − 70.804 to − 41.768, P < 0.001; β = − 0.265, 95% CI − 65.192 to − 36.550, P < 0.001, respectively). Likewise, when eGFRcrea-cyst was treated in place of eGFRcrea, this result was replicated in the correlation and regression analyses. Galectin-3 concentration was negatively associated with eGFR in patients with T2DM, independent of albuminuria status.

Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization

BackgroundNew-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear.ObjectiveThe present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF.MethodsA total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured.ResultsPost-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF.ConclusionsPlasma Gal-3 concentration is an independent predictor of post-MI NOAF.

Levels of Galectin-3 in Chronic Heart Failure: A Case-Control Study.

IntroductionHeart failure (HF) is a progressive clinical syndrome resulting from various cardiac disorders. Galectin-3 promotes adverse cardiac remodeling leading to chronic heart failure (CHF).AimTo estimate the levels of galectin-3 in chronic heart failure (CHF) patients and controls and to determine the association between galectin-3 levels with age, gender, and left ventricular ejection fraction (LVEF).Materials and methodsThe levels of plasma galectin-3 were estimated in CHF patients from January 2013 to October 2013 at Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu. The study was a case-control study. A total of 55 CHF patients were recruited as cases, and 55 controls were enrolled for the study. Participants' profiles were documented, and 5 mL of blood sample was collected. Galectin-3 levels in plasma were estimated by using an enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS 25.0 version. Mean, SD, and percentages were used to compare the characteristics of the two groups. The student's t-test was used to compare galectin-3 levels between CHF patients and the controls. ANOVA was employed to compare galectin-3 levels in the different age groups, gender, and LVEF. The receiver operating characteristic (ROC) curve was plotted for plasma galectin-3 in CHF.ResultsIn the present study, the mean age of CHF patients was 55.9±8.1 years and 54.1±9.4 years for controls. Males constituted 63.6% (n=35) and females were 36.4% (n=20) in the CHF group while 67.3% (n=37) were males and 32.7% (n=18) were females in the control group. The mean and SD for plasma galectin-3 was 9.95±2.8 ng/mL among CHF patients, while it was 4.08±1.3 ng/mL among controls (p<0.0001). As the age increased, levels of plasma galectin-3 increased in CHF patients and controls (p<0.00001). However, there was no statistical significance (p >0.05) for levels of galectin-3 among males and females in both groups. There was a highly significant difference in galectin-3 levels among cases and controls when classified into sub-groups based on their LVEF (p<0.0001). At the cut-off level of 8 ng/mL, plasma galectin-3 had a sensitivity of 92% and specificity of 71% in predicting CHF.ConclusionGalectin-3 helps in identifying CHF due to maladaptive remodeling of the heart. The present study concludes that estimating the plasma levels of galectin-3 is useful in diagnosing CHF.

Diagnostic Value of Galectin-3 for Identifying Acute Pulmonary Embolism in the Emergency Department

BackgroundPulmonary embolism (PE) is a common disease associated with high mortality and morbidity. Diagnosing PE is challenging due to diverse clinical presentations and the lack of specific biomarkers. ObjectiveWe hypothesized that plasma galectin-3 (Gal-3) levels might reflect the severity of acute PE and be useful for diagnostic assessment. MethodsIn this prospective study, 150 patients (100 patients with PE and 50 control patients) were included. Patients were stratified into high-risk, medium-risk, and low-risk groups according to the Wells and revised Geneva scoring systems, and Gal-3 levels were compared among the groups. PE was diagnosed by means of computed tomography pulmonary angiography. ResultsIn this study, of the 100 PE patients included in the study, 69 patients recovered and were discharged and 31 patients died. Median Gal-3 value in the PE group was 27.0 ng/mL (range 11.5–35.0 ng/mL), whereas the median Gal-3 value in the control group was significantly lower at 8.8 ng/mL (range 1.0–21.0 ng/mL) (p < 0.001). When the Gal-3 values of the PE group and the control group were evaluated with the receiver operator characteristic curve, the area under the curve was calculated as 0.99 (95% confidence interval 0.979–1). At a Gal-3 cutoff value of 13.55 ng/mL, which was determined to be the most appropriate value for PE diagnosis, the sensitivity was 98% and the specificity was 92%. ConclusionsA biomarker that rapidly and accurately diagnoses acute PE in the emergency department can be an extremely useful tool. We concluded that plasma Gal-3 levels can be regarded as a promising marker of acute PE.

Predictive Value of Galectin-3 and Brachial-Ankle Pulse Wave Velocity for Coronary Artery Calcification in Coronary Arteriography Patients

Objectives To study the predictive value for coronary artery calcification (CAC) of plasma galectin-3 and brachial-ankle pulse wave velocity (BaPWV) in coronary arteriography (CAG) patients. Methods Patients who received coronary arteriography (CAG) examination were recruited. The level of plasma galectin-3 was measured by the enzyme-linked immunosorbent assay. The arterial stiffness was analyzed by BaPWV and ankle-brachial index (ABI) which were measured using a volume-plethysmographic device. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of galectin-3 or BaPWV for coronary artery calcification (CAC). Results The level of galectin-3 and BaPWV was significantly higher in CAC patients compared with that in control (p < 0.01). The level of plasma galectin-3 was positively correlated with BaPWV (r = −0.296, p < 0.01) and negatively correlated with ABI (r = −0.296, p < 0.01). ROC curve analysis revealed that galectin-3 ≥5.90 ng/ml was the most powerful predictor for CAC with sensitivity of 85.5% and specificity of 83.5%. The area under the curve (AUC) was 0.916. When the level of BaPWV was more than 1909 m/s, the sensitivity and specificity were 61.8% and 69.6%, respectively, for predicting CAC. The AUC was 0.646. Conclusions The level of plasma galectin-3 increases significantly in CAC patients compared to control, and its level is related to BaPWV and ABI. Galectin-3 and BaPWV can be used to predict CAC, and the diagnosis value (sensitivity and specificity) of galectin-3 for CAC is better than that of BaPWV.

Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression.

Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6–510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85–7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.

Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study.

Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis. A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1-/- mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca2+ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE-/- mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia-reperfusion injury in ApoE-/- mice. Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels.

Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

BackgroundGalectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages.MethodsThis is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition.ResultsTwo thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI95% [0.74–0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI95% [1.68–1.93], p < 0.001, non-adjusted and OR 1.37 CI95% [1.27–1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screatadm, pNGAL with a NRI of 0.27 CI95%(0.16–0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively).ConclusionPlasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission.Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011.Graphical abstract

Profile of Plasma Galectin-3 Concentrations, Inflammatory Cytokines Levels and Lymphocytes Status in Breast Cancer under Chemotherapy

We investigated relationship between galectin-3 (Gal-3) levels and T lymphocytes apoptosis and the activation rates in breast cancer during chemotherapy. We used plasma samples from 112 women classified into two groups: 70 women with breast cancer (BC) and submitted to neoadjuvant chemotherapy (3 cycles) and 42 healthy women used as controls. In the group of BC, blood samples were taken before each cycle of chemotherapy and Gal-3 levels was evaluated by ELISA sandwich. Flow cytometry was used to study T cells apoptosis and activation. Before treatment, median value of Gal-3 was 6.31 ng/ml (range 1.07 - 50.74) in BC and 0.84 ng/ml (range 0.00 - 4.82) in HC. Gal-3 levels were highest in plasmas from BC (p p p = 0.010). In addition, we found a dynamic relationship between gal-3 levels, tumor size and T lymphocytes apoptosis rates during treatment depending to the cure efficiency. We suggest gal-3 plasma concentrations could be used as predictive biomarker for chemotherapy efficiency in breast cancer patients.

Alterations of Plasma Galectin-3 and C3 Levels in Patients with Parkinson's Disease.

Parkinson’s disease (PD) is characterized by progressive neurodegeneration of dopaminergic neurons in the ventral midbrain. The complement-phagosome pathway is involved in the pathogenesis of PD. Here we measured levels of complement-phagocytosis molecules, including galectin-3, C3, C4, and cathepsin D, in the plasma of 56 patients with PD, and 46 normal controls (NCs). Plasma levels of galectin-3 (9.93 ± 3.94 ng/mL) were significantly higher in PD patients compared with NCs (8.39 ± 1.95 ng/mL, p = 0.012), and demonstrated a positive correlation with Hoehn and Yahr stages in PD patients (R2 = 0.218, p < 0.001). On the other hand, plasma C3 levels were significantly lower in PD patients (305.27 ± 205.16 μg/mL) compared with NCs (444.34 ± 245.54 μg/mL, p = 0.002). However, the levels did not correlate with Hoehn and Yahr stages (R2 = 0.010, p = 0.469). Plasma levels of C4 and cathepsin D in PD patients were similar to those in NCs. Our results show possible altered complement-phagocytosis signals in the peripheral blood of PD patients, highlighting the potential of galectin-3 as a biomarker of PD.

Novel plasma biomarkers predicting biventricular involvement in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular involvement in ARVC may lead to heart failure. This study aimed to investigate the role of plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting biventricular involvement and adverse outcomes in ARVC. ARVC patients from 2 independent cohorts, were studied. The Bejing (Chinese) cohort (n=108) was the discovery cohort, whereas the Zurich (Swiss) cohort (n=47) served as validation. All patients had a definite ARVC diagnosis at time of blood withdrawal. Biomarkers were independently correlated with NT-proBNP and left ventricular (LV)-function. ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricle (RV) involvement. sST2 and GDF-15 were significantly correlated with late gadolinium enhancement in CMR and with adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement. The combined use of the three biomarkers (sST2, GDF-15 and NT-proBNP) showed the best performance in predicting LV involvement in both cohorts. Plasma drawn from the coronary arteries and coronary sinus indicated a transmyocardial elevation of sST2, but no transmyocardial gradient of GDF-15. After heart transplantation, both sST2 and GDF-15 returned to near-normal levels. Our study showed that sST2 and GDF-15 may predict biventricular involvement in ARVC. The combined use of sST2, GDF-15 and NT-proBNP showed the best prediction of biventricular involvement in ARVC.

MiR-339 and galectin-3: diagnostic value in patients with airway obstruction after lung transplantation.

Respiratory complications can be the cause of graft dysfunction after lung transplantation (LTx). MicroRNAs are small regulatory molecules-potential biomarkers of respiratory diseases and post-transplant complications. Galectin-3 is highly expressed in fibrosis of transplanted solid organs. The aim was to evaluate the expression of plasma miR-339 and galectin-3 concentrations in lung recipients including with airway obstruction after LTx. The study included 57 lung recipients (34 men and 23 women aged 10 to 74years) were followed up to 5years after LTx. The plasma microRNAs were detected by real-time PCR; galectin-3 levels were measured by ELISA. During follow-up in 30 recipients, post-transplant complications were detected: 12 (40.0%) cases of airway obstruction. The levels of miR-339 and galectin-3 were significantly higher in recipients with airway obstruction compare with 27 (47.3%) recipients without any complications (P=0.036 and P=0.014, resp.). Increasing miR-339 (above the 0.02 fold change) and galectin-3 (above the 11.7ng/ml) threshold plasma levels in lung recipients is associated with high risk (RR=7.14±0.97 [95% CI 1.05-48.60], P=0.045) of airway obstruction after LTx. A measurement of miR-339 expression in combination with galectin-3 level might be perspective to identify recipients at risk of airway obstruction after LTx.

Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients.

Galectin-3 reportedly participates in the inflammatory process that causes insulin resistance in the target tissues. However, the role of high plasma galectin-3 levels as an indicator of protein-energy wasting (PEW) in patients undergoing maintenance hemodialysis remains unclear. This study included 240 hemodialysis patients (64.5 [55.3−74.0] years, 35.8% women) from a tertiary medical center. A baseline assessment of demographic and clinical data, biochemical parameters, and body composition was conducted. Plasma galectin-3 and other biomarkers were measured using a multiplex bead-based immunoassay. Participants were then divided into two subgroups depending on the median value of plasma galectin-3. Malnutrition was identified using the geriatric nutritional risk index (GNRI) and the criteria of the International Society of Renal Nutrition and Metabolism. Independent risk factors for elevated plasma galectin-3 and malnutrition were identified by multivariate logistic regression. The high galectin-3 group was more likely to be older, have lower lean tissue mass and GNRI scores, be diagnosed with PEW, dialyze through a tunneled catheter, and have higher circulating IL-6, TNF-α, and MCP-1 concentrations than the low galectin-3 group. After multivariate adjustment, only low mean arterial pressure, dialyzing with tunneled cuffed catheters, and elevated systemic inflammatory markers correlated with high galectin-3 levels. Plasma galectin-3 concentrations also increased significantly in hemodialysis patients with PEW. However, compared with other commonly used nutritional indicators, galectin-3 did not show superiority in predicting PEW. Although the plasma galectin-3 levels correlated with PEW severity, this correlation disappeared after adjustment for potential confounding variables (OR, 1.000; 95% CI, 0.999–1.001). In conclusion, plasma galectin-3 is a valuable biomarker for systemic inflammation but is less prominent for PEW in patients with maintenance hemodialysis. Further identification of novel biomarkers is required to detect patients at risk for malnutrition and implement appropriate interventions.

Galectin-3 is inversely associated with cardiorespiratory fitness in the general population

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Low cardiorespiratory fitness (CRF) is associated with high mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis, different cancers, renal impairment and, in particular, for heart failure. Further, higher Gal-3 levels are associated with increased cardiovascular mortality. Whether Gal-3 is related with the protective effects of a high CRF is unclear. Purpose The present study examined the relation between Gal-3 and CRF as determined by body weight adjusted peak oxygen uptake (VO2peak/kg), oxygen uptake at the anaerobic threshold (VO2@AT) and maximal workload (Wmax). Methods We used data of the population-based Study of Health in Pomerania (SHIP-TREND) from Northeast Germany. A total of n = 1,483 participants with a median age of 49 (IQR: 39 – 59 years, male 48%) were included in the analysis. CRF parameters were measured using standardized cardiopulmonary exercise testing on a bicycle ergometer. Plasma galectin-3 concentrations were determined using a quantitative sandwich enzyme immunoassay. Individuals with left ventricular ejection fraction &amp;lt; 40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (eGFR &amp;lt; 30 ml/min/mm2), a history of cancer, and extreme values for Gal-3 were excluded. Linear regression models adjusted for age, sex and lean mass were used to analyze the association between Gal-3 and CRF. Results A one ml/min/kg greater VO2peak was related to a 0.32 ng/ml (95% confidence interval [CI] -0.45 to -0.18, p &amp;lt;.001) lower Gal-3. Further, a one Watt larger power output was also associated with a 1.32 ng/ml (95% CI -2.10 to – 0.54, p &amp;lt;.001) lesser Gal-3. VO2@AT was not related to Gal-3 (β: -3.31 95% CI -8.68 to 2.05, p = .23). Conclusions In the general population Gal-3 is inversely associated with CRF. Further studies should investigate whether lower Gal-3, beyond its importance as a biomarker for heart disease, may even play a role in the protective effect of the CRF.