Higher Galectin-3 Levels Research Articles

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma.

Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015). Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Higher Serum Galectin‑3 Levels Were Associated with More Severe Motor Performance in Parkinson's Disease.

Parkinson's disease (PD) is a movement disorder that lacks proven biomarkers. Case-control genome-wide association studies revealed the potential effect of galectin‑3 (GAL3) on motor progression in PD patients. Based on this finding, our study aimed to explore the correlation between serum GAL3 levels and motor performance in PD patients. Five hundred PD patients and 200healthy controls were recruited. The serum levels of GAL3 were measured in participants by enzyme linked immunosorbent assay (ELISA). The baseline characteristics of the participants were collected, and the associated scale scores were obtained. Compared with healthy controls, the serum levels of GAL3 were greatly increased in PD patients. These levels could distinguish between PD patients and healthy controls with a sensitivity of 0.798 and a specificity of 0.815 (AUC = 0.795, 95% CI 0.757-0.834, P < 0.001). Patients with age >60 years tended to have higher serum GAL3 levels, disease duration, Hoehn-Yahr stage, MDS-UPDRS III total score, tremor subscores, rigid subscores, and bradykinesia subscores than those with age ≤60 years. When adjusting for confounders, higher GAL3 level was significantly correlated with MDS-UPDRS III total score and rigid subscores. In men with PD, GAL3 was significantly correlated with MDS-UPDRS III total score; but the association between GAL3 and bradykinesia subscores was found in women. Moreover, the associations between GAL3 with MDS-UPDRS III total score and bradykinesia subscores were significant in patients with age >60 years. Higher GAL3 level was related to more severe motor performance in patients with age >60 years, and it may be a potential predictive biomarker for motor performance in PD patients.

Galectin-3 modulates microglial activation and neuroinflammation in early brain injury after subarachnoid hemorrhage

BackgroundAneurysmal subarachnoid hemorrhage (SAH) is a devastating acute cerebrovascular event with high mortality and permanent disability rates. Higher galectin-3 levels on days 1–3 have been shown to predict the development of delayed cerebral infarction or adverse outcomes after SAH. Recent single-cell analysis of microglial transcriptomic diversity in SAH revealed that galectin could influence the development and course of neuroinflammation after SAH. MethodsThis study aimed to investigate the role and mechanism of galectin-3 in SAH and to determine whether galectin-3 inhibition prevents early brain injury by reducing microglia polarization using a mouse model of SAH and oxyhemoglobin-treated activation of mouse BV2 cells in vitro. ResultsWe found that the expression of galectin-3 began to increase 12 h after SAH and continued to increase up to 72 h. Importantly, TD139-inhibited galectin-3 expression reduced the release of inflammatory factors in microglial cells. In the experimental SAH model, TD139 treatment alleviated neuroinflammatory damage after SAH and improved defects in neurological functions. Furthermore, we demonstrated that galectin-3 inhibition affected the activation and M1 polarization of microglial cells after SAH. TD139 treatment inhibited the expression of TLR4, p-NF-κB p65, and NF-κB p65 in microglia activated by oxyhemoglobin as well as eliminated the increased expression and phosphorylation of JAK2 and STAT3. ConclusionThese findings suggest that regulating microglia polarization by galectin-3 after SAH to improve neuroinflammation may be a potential therapeutic target.

Association of serum galectin-3 levels with mortality and cardiovascular disease outcomes in hemodialysis patients: a systematic review and dose–response meta-analysis

BackgroundGalectin-3 has been proposed as a candidate marker for cardiovascular risk stratification, although its role in kidney failure is unclear. The aim of this systematic review was to assess the association of serum galectin-3 levels with overall survival and cardiovascular outcomes among hemodialysis patients.MethodsMedline, Scopus, Web of Science and CENTRAL were systematically searched from inception till Aug 20, 2023. Observational studies evaluating the association of serum galectin-3 with mortality, cardiovascular disease and arterial stiffness in hemodialysis patients were included. The exposure–response relationship between galectin-3 and mortality was explored by dose–response meta-analysis using restricted cubic splines in a one-stage approach.ResultsOverall, 13 studies were included (9 cohort and 4 cross-sectional), comprising 6025 hemodialysis individuals. Increasing galectin-3 values were associated with greater all-cause mortality risk (χ2: 18.71, p-value < 0.001) and an insignificant trend toward higher cardiovascular mortality risk (χ2: 5.06, p-value: 0.079). Compared to a reference galectin-3 value of 10 ng/ml, all-cause mortality risk was significantly higher with levels of 20 ng/ml (Hazard ratio–HR: 2.62, 95% confidence intervals-CI: 1.66–4.15), 30 ng/ml (HR: 3.78, 95% CI: 2.05–6.97) and 40 ng/ml (HR: 4.01, 95% CI: 2.14–7.52). Qualitative synthesis of evidence indicated that serum galectin-3 may be linked to abdominal aortic calcification severity and progression, as well as to left ventricular systolic and diastolic dysfunction.ConclusionsThis study suggests that high serum galectin-3 levels are associated with greater all-cause mortality risk among patients on maintenance hemodialysis. Preliminary cross-sectional evidence indicates that serum galectin-3 may be associated with arterial stiffness and left ventricular dysfunction.

Soluble galectin-3 as a microenvironment-relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma.

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more TREGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD.

The prognostic role of galectin-3 and endothelial function in patients with heart failure.

Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group. Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Correlation Analysis of Galectin-3 Serum Level in Obesity with and without Obesity

There are more than 3.4 million deaths every year in the world due to overweight and obesity. Obesity is a chronic proinflammatory condition marked by increased lipid and adipose tissues, leading to ectopic fat accumulation with increased levels of proinflammatory cytokines. Obesity causes a progressive increase in galectin-3 expression, especially in visceral and subcutaneous adipose tissue in experimental animals. Galectin-3 is upregulated in obesity and is defined as a proinflammatory molecule that can cause insulin resistance. This study aims to analyze differences in galectin-3 levels between obese and non-obese subjects. This was a cross-sectional study, using a total of 80 subjects. The study was conducted throughout August 2022. The samples were grouped into obese and non-obese based on Body Mass Index (BMI). The galectin-3 measurement used the Enzyme-Linked Immunosorbent Assay (ELISA) method. Statistical tests used the Mann-Whitney test and Spearmen rho; the test results were significant if the p-value &lt;0.05. The samples were divided into obese and non-obese groups, each group had 40 people. Galectin-3 levels in the obese group were 0.9±0.36 ng/mL significantly higher than the non-obese group’s 0.43±0.11 ng/mL, (p&lt;0.001). There was a strong positive correlation between levels of galectin-3 and BMI, (r=0.866, p&lt;0.001). There is a positive correlation between serum galectin-3 levels and BMI. The greater value of the BMI, the higher levels of galectin-3.

Inflammation biomarkers are associated with the incidence of cardiovascular disease: a meta-analysis.

Inflammation is a risk factor for cardiovascular disease (CVD), and particular inflammatory parameters can be used to predict the incidence of CVD. The aim of this study was to assess the association between fibrinogen (FIB), interleukin-6 (IL-6), C-reactive protein (CRP) and galectin-3 (Gal-3) and the risk of cardiovascular disease using meta-analysis. PubMed, Embase, Scopus, and Web of Science databases were searched with the appropriate strategies to identify observational studies relevant to this meta-analysis. A random-effects model was used to combine inflammation factor-associated outcomes and cardiovascular disease outcomes, except in the case of galectin-3, where a fixed-effects model was used because of less heterogeneity. Location, age, type of cardiovascular disease, and sample size factors were used to explore heterogeneity in stratification and metaregression for subgroup analysis. A case-by-case literature exclusion approach was used for sensitivity analysis. The funnel plot and Begg's test were combined to assess publication bias. Thirty-three papers out of 11,456 were screened for inclusion in the analysis. Four inflammation biomarkers were significantly associated with the development of CVD: FIB (OR: 1.21, 95% CI: 1.15-1.27, P < 0.001; HR: 1.04, 95% CI: 1.00-1.07, P < 0.05), IL-6 (HR: 1.16, 95% CI: 1.10-1.22, P < 0.001), CRP (OR: 1.25, 95% CI: 1.15-1.35, P < 0.001; HR: 1.20, 95% CI: 1.14-1.25, P < 0.001) and Gal-3 (HR: 1.09, 95% CI: 1.05-1.14, P < 0.001). Location factors help explain the source of heterogeneity, and there is publication bias in the Gal-3 related literature. Taken together, the current research evidence suggests that high levels of fibrinogen, interleukin-6, C-reactive protein and galectin-3 are risk factors for cardiovascular disease and can be used as biomarkers to predict the development of cardiovascular disease to some extent. https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023391844.

Higher Levels of Galectin-1 and Galectin-3 in Young Subjects with Autism Spectrum Disorder Compared to Unaffected Siblings and Healthy Controls.

: Despite being highly genetic, the etiology of autism spectrum disorder (ASD), has not yet been clarified. Recent research has focused on the role of neuroinflammation and immune system dysfunction in the pathophysiology of neurodevelopmental disorders including ASD. Galectin-1 and galactin-3 are considered among the biomarkers of neuroinflammation and there has been recent reports on the potential role of galectins in the etiology of neurodevelopmental disorders. However, there has been no study examining the relationship between ASD and galectin levels. : Current study aimed to investigate galectin-1 and galectin-3 serum levels in young subjects with ASD comparing with their unaffected siblings and healthy controls. : We found significantly higher levels of galectin-1 in case group compared to both unaffected siblings and healthy controls, and higher levels of galectin-3 in case group compared to healthy controls. However, there was no significant association between galectin-1 and galectin-3 levels with the severity of ASD. : Findings of our study may support neuroinflammation hypothesis in the etiology of ASD and the potential role of galectin-1 and galectin-3 as biomarkers.

Plasma Galectin-3 Biomarkers in Chronic Kidney Disease

Assessment of renal function is based on determination of serum creatinine and creatinine-based equations to assess GFR. However, this marker is not perfect or accurate, especially for longitudinal monitoring of kidney function in Chronic Kidney Disease (CKD patients). Decreased kidney function can be slowed or even anticipated with early detection, so as to avoid secondary complications. So it is important to find new biomarkers that can identify individuals at risk as early as possible. Plasma galectin-3 is a ?-galactoside-binding lectin expressed in monocytes, which plays an important role in inflammation, immunity, cancer, and is involved in the pathogenesis of atherosclerosis, diabetes, renal fibrosis and asthma. Higher galectin-3 levels were associated with reduced eGFR in a cross-sectional study. Galectin-3 is essential in various biological activities including cell growth, cell proliferation, differentiation, apoptosis, pre-mRNA splicing, transformation, angiogenesis, inflammation, fibrosis, fibrogenesis and host defense. Galectin-3 is a stable biomarker and is not associated with age, body mass index or sex. Galectin-3 is also useful for detecting the early stages of some diseases. Galectin-3 shows no circadian variation and increases slightly after exercise, returning to normal levels after 1-3 hours. Higher concentrations of galectin-3 may be associated with CKD development, indicating the potential for new mechanisms related to galectin-3 expression that may contribute to CKD development. Galectin-3 has also been reported to play an important role in renal interstitial fibrosis. Thus, galectin-3 inhibition may be a promising therapeutic strategy to prevent kidney disease progression.

Short and Long-Term Prognostic Significance of Galectin-3 in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

This study evaluated the short and long-term prognostic value of galectin-3 in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Patients (n = 143) were admitted with STEMI and followed up for 2years. The study population was divided into high and low galectin-3 groups based on the admission median value of serum galectin-3. Primary clinical outcomes consisted of cardiovascular (CV) mortality, non-fatal reinfarction, stroke, and target vessel revascularization (TVR). CV events were recorded in hospital and at 1 and 2years. The primary clinical outcomes (in-hospital, 1year and 2year) were significantly higher in the high galectin-3 group. (P = .008, P = .004, P = .002, respectively). High galectin-3 levels were also associated with heart failure development and re-hospitalization at both 1year (P = .029, P = .009, respectively) and 2years (P = .019, P = .036, respectively). According to Cox multivariate analysis, left ventricular ejection fraction (LVEF) was an independent predictor of 2-year cardiovascular mortality (P = .009), whereas galectin-3 was not (P = .291). Although high galectin-3 levels were not independent predictors of long-term CV mortality in patients with acute STEMI who underwent primary PCI, it was associated with short-term and long-term development of adverse CV events, heart failure, and re-hospitalization.

Serum galectin-3 levels predict poor prognosis in sepsis and septic shock patients.

Sepsis and septic shock are clinical conditions with high mortality and an ever-increasing prevalence, and early diagnosis is of great importance in treating these diseases. Increase in serum Galectin-3 protein in septic patients is associated with increased inflammation, which in turn is associated with mortality. This study aimed to investigate the diagnostic importance of serum Galectin-3 levels and its relationship with in-hospital mortality in sepsis and septic shock patients. This prospective cohort study included 44 sepsis and 44 septic shock patients. Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation 2 score were calculated. In addition, routine clinical and laboratory parameters along with serum Galectin-3 were evaluated. Serum Galectin-3 levels were significantly higher in the septic shock group [4.1 (0.1-10.2) vs. 6.0 (0.1-11.3) ng/mL, respectively; p=0.01]. Moreover, patients with a Galectin-3 level <6.94 ng/mL were associated with longer survival [31.4 vs. 23.1 days; hazards ratio, 1.85; 1.03-3.34, p=0.03]. More importantly, the need for mechanical ventilation, the duration of mechanical ventilation, and serum Galectin-3 levels were independent prognostic factors and predicted poor in-hospital survival in both sepsis and septic shock patients. These findings suggest that Galectin-3 levels are higher in septic shock patients and predict mortality. In addition, high serum Galectin-3 levels, together with mechanical ventilation requirement and mechanical ventilation duration, are closely associated with poor in-hospital survival. Therefore, Galectin-3 may be a valuable diagnostic and prognostic biomarker in these patients.

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure

Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

The prognostic role of galectin-3 and endothelial function in patients with heart failure according to left ventricular ejection fraction classification HF group

Abstract Background Heart failure (HF) is nowadays classified in HF with reduced ejection fraction (HFrEF), HF with mildly-reduced EF (HFmrEF) and HF with preserved EF (HFpEF). Endothelial dysfunction, increased arterial stiffness and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. Purpose The purpose of this prospective, follow-up study was to investigate in patients with stable ischemic HF the prognostic role of circulating galectin-3 levels, endothelial function and arterial stiffness according to left ventricular ejection fraction classification. Methods In this study we prospectively enrolled 340 patients with stable ischemic HF. Patients were categorized in HFrEF (when EF below or equal to 40%), HFmrEF (when EF is more than 40%&amp;lt;ef≤49%)&amp;gt; and below/equal to 49%) and HFpEF (when EF is more/equal to 50% along with the presence of structural or functional dysfunction and/or elevated natriuretic peptides) according to recent guidelines upon 2D echocardiographic assessment. We evaluated flow-mediated dilatation (FMD) of brachial artery as a marker of endothelial function, carotid-femoral pulse-wave velocity (PWV) as a marker of arterial stiffness and galectin-3 levels as a biomarker of fibrosis. Patients were followed-up for MACE and the primary endpoint was defined as cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization due to HF. &amp;lt;ef≤49%)&amp;gt; Results Interestingly, FMD values exhibited a stepwise improvement according to LVEF (HFrEF: 4.74±2.35% vs. HFmrEF: 4.97±2.81% vs. HFpEF: 5.94±3.46%, p=0.01) which remained statistically significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% CI: 0.166–1.814, p=0.019). Multivessel coronary artery disease (CAD) was more frequent in the group of HFrEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p=0.049). Nevertheless, PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51±2.35% vs. 5.32±2.67%, p=0.02) and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p=0.01). Conclusions FMD values have a linear improvement according to LVEF increase in patients with ischemic HF and worse values are linked to more MACEs. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF. Funding Acknowledgement Type of funding sources: None.

CORRELATION OF SERUM GALECTIN-3 LEVELS WITH EJECTION FRACTIONS IN HEALTHY SUBJECTS AND HEART FAILURE PATIENTS

Background: High Galectin-3 levels are indicative of severity of heart diseases and are associated with increased risk of major adverse cardiovascular events including heart failure. The objective of this study was to determine correlation between ejection fraction and serum Galectin-3 levels recorded by simple and quick test. Methods: This cross-sectional analytical study was conducted at the Armed Forces Institute of Cardiology (AFIC) Rawalpindi. Thirty (30) healthy adults and 60 heart failure patients were selected through randomised sampling. Diagnosed cases were classified using modified NYHA classification. Group 1 included healthy adults, Group 2 included 30 mild heart failure subjects of NYHA class I and II, Group 3 included 30 severe heart failure subjects of NYHA class III and IV. Ejection fraction was recorded at AFIC with trans-thoracic echocardiography in supine and left lateral positions. Blood samples of the participants were used for estimation of Galectin-3 by ELISA using human serum Galectin-3 ELISA kit Catalogue No. E1951Hu (Bio Assay technology). Observations were recorded on proforma, Pearson’s correlation test and ANOVA were performed using SPSS-24. Results: The LVEF was 70.7±2.78% in Group-1, 59.3±3.4% in Group-2, and 38.96±12.27% in Group-3. The LVEF showed a substantial negative correlation with serum Galectin-3 levels (r= -0.630, p&lt;0.001). Conclusion: There is a significant negative correlation between Serum Galectin-3 and extent of functional changes of left ventricle recorded by Ejection fraction on echocardiography. Pak J Physiol 2022;18(2):28–30

Galectin-3 in Patients from 2012-2020: A Prognostic Biomarker of Left Ventricular Assist Device Post Implantation Outcomes

Purpose Galectin-3 is a novel biomarker that has been used to risk stratify patients with heart failure. Elevated levels with values greater than 25.9 ng/mL are linked with poor outcomes and higher cardiovascular risk, however, outcomes in Left Ventricular Assist Device (LVAD) patients have not been well explored. We sought to investigate the relationship between Galectin-3 and outcomes in the LVAD population. Methods From 2012 to 2020, 249 patients with heart failure at our institution had lab values collected for Galectin-3. Among them, 171 patients underwent LVAD implantation. Lab and hemodynamic values, including Galectin-3, Creatinine, and PAPI, were collected for all patients prior to LVAD implant. Post-LVAD outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length of ICU stay, and mortality were collected. Results There was no significant correlation between age, BMI, BSA and Galectin-3 (Table 1). Patients who experienced RVF (n=59) had a higher mean Galectin-3 compared to those who did not (n=112), with 30.9 ng/mL ± 15.21 compared to 24.9 ng/mL ± 10.7 (p=0.004). Those who received an RVAD (n=18) had higher Galectin-3 levels with mean 28.8 ng/mL ± 12.87 than those that did not (n=153) with mean 26.9 ng/mL ± 12.89 (p=0.558). Galectin-3 was positively correlated with inotrope duration (r=0.306, p=0.001), Creatinine (r=0.278, p=0.001) and length of ICU stay (r=0.191, p=0.022). Galectin-3 levels in patients who died (n=73) were higher than in those who did not (n=98), with a mean of 28.95 ng/mL ± 13.25 compared to 25.73 ng/mL ± 12.38 (p=0.11). Galectin-3 was negatively correlated to PAPI (r=-0.177, p=0.05), but was not significantly correlated to other hemodynamic parameters. Conclusion The Galectin-3 biomarker can be used as a predictor of post-LVAD implantation outcomes, elevated levels being associated with RVF, longer time on inotropes, increased length of ICU stay, decreased PAPI, and elevated creatinine. Galectin-3 is a novel biomarker that has been used to risk stratify patients with heart failure. Elevated levels with values greater than 25.9 ng/mL are linked with poor outcomes and higher cardiovascular risk, however, outcomes in Left Ventricular Assist Device (LVAD) patients have not been well explored. We sought to investigate the relationship between Galectin-3 and outcomes in the LVAD population. From 2012 to 2020, 249 patients with heart failure at our institution had lab values collected for Galectin-3. Among them, 171 patients underwent LVAD implantation. Lab and hemodynamic values, including Galectin-3, Creatinine, and PAPI, were collected for all patients prior to LVAD implant. Post-LVAD outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length of ICU stay, and mortality were collected. There was no significant correlation between age, BMI, BSA and Galectin-3 (Table 1). Patients who experienced RVF (n=59) had a higher mean Galectin-3 compared to those who did not (n=112), with 30.9 ng/mL ± 15.21 compared to 24.9 ng/mL ± 10.7 (p=0.004). Those who received an RVAD (n=18) had higher Galectin-3 levels with mean 28.8 ng/mL ± 12.87 than those that did not (n=153) with mean 26.9 ng/mL ± 12.89 (p=0.558). Galectin-3 was positively correlated with inotrope duration (r=0.306, p=0.001), Creatinine (r=0.278, p=0.001) and length of ICU stay (r=0.191, p=0.022). Galectin-3 levels in patients who died (n=73) were higher than in those who did not (n=98), with a mean of 28.95 ng/mL ± 13.25 compared to 25.73 ng/mL ± 12.38 (p=0.11). Galectin-3 was negatively correlated to PAPI (r=-0.177, p=0.05), but was not significantly correlated to other hemodynamic parameters. The Galectin-3 biomarker can be used as a predictor of post-LVAD implantation outcomes, elevated levels being associated with RVF, longer time on inotropes, increased length of ICU stay, decreased PAPI, and elevated creatinine.

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.

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.

EXTH-72. TRANSLATIONAL INVESTIGATION OF TD139 FOR THE TREATMENT OF HIGH-GRADE MENINGIOMA

Abstract BACKGROUND High-Grade Meningioma (HGM), such as atypical and anaplastic meningiomas, represent a subgroup of meningiomas with histologic and clinical features suggesting aggressive behavior with a penchant for recurrence, even after surgical resection. Here, we postulate that high levels of Galectin-3 (Gal-3) affect the cellular composition and are at the root of the profoundly immunosuppressive tumor microenvironment of HGM. Our study aimed to validate the effect of the Gal-3 inhibitor (TD139) in in vivo. METHODS In vivo MGS2 murine models of HGM were utilized to assess efficacy of treatment with TD139 via intravenous injection. We used ELISA spot, RT-PCR and western blots techniques. MRI and immunohistochemistry -staining methods were used to detect tumor growth in in vivo following TD139 treatments. RESULTS Our results demonstrated a significantly elevated level of Gal-3 in both HGM tissue and serum when compared to non-tumor patients. Furthermore, Epithelial membrane antigen, Ki-67, and Transglutaminase 2 were highly expressed in HGM, whereas the number of observed cytotoxic T-cells in HGM was markedly decreased. When human PBMCs were activated with anti-CD3 (1µg/ml) and anti-CD28 (2µg/ml) antibodies and treated with recombinant Gal-3 protein (500ng/ml) for 96hr, we found reduced expression of T-Box Transcription Factor 21 and RAR Related Orphan Receptor C mRNA with concurrent upregulated expression of GATA Binding protein 3 and Forkhead box P3 mRNA. These findings support the concept that Gal-3 skews the differentiation of CD4+ T cells towards Th2 and Treg cells. In vivo treatment of TD139 (1mg/kg per day for 14 days) showed significant decrease (∼35%) in MGS2 tumor growth in orthotopic allograft model (at Day 41) and increased survival via multiple mechanism. Additionally, we observed an upregulation of CD38 (M1 macrophages) and CD8+ T cells in treated cells. CONCLUSIONS These findings suggest that TD139 may be an effective approach in the treatment of HGM patients.

Galectin-3, metalloproteinase-2 and cardiovascular disease were independently associated with metalloproteinase-14 in patients with type 1 diabetes: a cross sectional study

BackgroundType 1 diabetes (T1D) is a major risk factor for cardiovascular disease (CVD). Matrix metalloproteinase-14 (MMP-14) is involved in the development of atherosclerosis and CVD. The main aim was to explore the associations between MMP-14 and selected inflammatory and metabolic variables, CVD, depression, physical activity, smoking and medication in patients with T1D. The secondary aim was to explore associations with CVD.MethodsCross-sectional design. The participants were consecutively recruited from one specialist diabetes out-patient clinic. Depression was assessed by a self-report instrument. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. High MMP-14 was defined as ≥ 5.81 ng/mL. Non-parametric tests, Chi2 tests and multiple logistic regression analyses were performed.ResultsTwo hundred and sixty-eighth T1D patients aged 18–59 years participated (men 58%, high MMP-14 25%, CVD 3%). Sixty-seven patients with high MMP-14, compared to 201 patients with lower MMP-14, had higher prevalence of CVD (8% versus 1%, p = 0.012), and had higher levels of galectin-3 (p < 0.001) and MMP-2 (p = 0.018). Seven patients with CVD, compared to 261 without, were older (p = 0.003), had longer diabetes duration (p = 0.027), and had higher prevalence of high MMP-14 (71% versus 24%, p = 0.012), abdominal obesity (p = 0.014), depression (p = 0.022), usage of antidepressants (p = 0.008), antihypertensive drugs (p = 0.037) and statins (p = 0.049).Galectin-3 (per ng/mL) [adjusted odds ratio (AOR) 2.19, p < 0.001], CVD (AOR 8.1, p = 0.027), and MMP-2 (per ng/mL) (AOR 1.01, p = 0.044) were associated with high MMP-14. Depression (AOR 17.4, p = 0.006), abdominal obesity (15.8, p = 0.006), high MMP-14 (AOR 14.2, p = 0.008), and diabetes duration (AOR 1.10, p = 0.012) were associated with CVD.ConclusionsThe main findings of this study were that galecin-3, MMP-2, and CVD were independently associated with high levels of MMP-14 in T1D patients. The association between MMP-14 and galectin-3 is a new finding. No traditional risk factors for CVD were associated with MMP-14. Depression, abdominal obesity and MMP-14 were independently associated with CVD.