Higher Galectin-3 Research Articles

Prognostic value of galectin-3 and right ventricular function for long-term mortality in heart failure patients treated with cardiac resynchronization therapy

Recently, associations between the biomarker galectin-3 and numerous pathological processes involved in heart failure (HF) and right ventricular (RV) function have been observed. We aimed to assess the long-term prognostic ability of galectin-3 and RV function parameters for all-cause mortality in HF patients treated with cardiac resynchronization therapy (CRT). We prospectively studied 63 symptomatic HF patients with a left ventricular (LV) ejection fraction (EF) ≤ 35%. The median serum galectin-3 concentration was 13.4 ng/mL (IQR 11.05, 17.15). A detailed assessment of LV and RV geometry and function was performed with echocardiography. CRT defibrillator implantation was achieved in all patients without major complications. The follow-up lasted 5 years. In the multivariable Cox regression model, independent predictors for all-cause mortality were log baseline galectin-3 and baseline RV function expressed as tricuspid annular plane systolic excursion with HR 2.96 (p = 0.037) and HR 0.88 (p = 0.023), respectively. Analysis of subgroups defined by galectin-3 concentration and CRT response showed that patients with high baseline galectin-3 concentrations and a lack of response to CRT had a significantly lower probability of survival. In our patient cohort, the baseline galectin-3 concentration and RV function were independent predictors of long-term all-cause mortality in HFrEF patients following CRT implantation.

Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis.

Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear.Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model.Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61–2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62–6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18–2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58–5.60, p = 0.001); but, high expression of galectin-4 and −9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36–0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44–0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19–0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37–0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79–4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23–0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15–2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91–27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57–4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61–9.99, p < 0.001).Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.

Galectin-3 for prediction of cardiac function compared to NT-proBNP in individuals with prediabetes and type 2 diabetes mellitus

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35–74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β − 0.36, 95% CI − 0.63/− 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β − 0.34, 95% CI − 0.53/− 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β − 0.656, 95% CI − 1.07/− 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HRperSD) 1.60, 95% CI 1.39–1.85; P < 0.0001) and all-cause mortality (HRperSD 1.36, 95% CI 1.25–1.47; P < 0.0001) in T2DM. No relationship between galectin-3 and cardiac function was found in euglycaemia, whereas NT-proBNP consistently related to reduced cardiac function. Prospective value of NT-proBNP on cardiovascular and all-cause mortality was higher. NT-proBNP was superior to galectin-3 to assess reduced systolic and diastolic function.

The association of galectin-3 level with ventricular arrhythmias and left ventricular strain in heart failure patients with implantable cardioverter defibrillator

Background Ventricular arrhythmias are life-threatening complications of heart failure (HF). Galectin-3, an indicator of fibrosis, is associated with incident HF and was found to be related to poor prognosis in these patients. We aimed to investigate the association of galectin-3 level with left ventricular (LV) arrhythmias in HF. Methods A total of 92 non-ischaemic HF patients who had implantable cardioverter-defibrillator were included in this study. Patients were divided into two groups based on the galectin-3 level. Ventricular arrhythmic events and LV strain indices were compared between the two groups. Negative binomial regression was used to detect the independent predictors of total arrhythmic events in HF patients. Results The median age was 65 (54–71) in the high galectin-3 group (HGAL) and 62 (52–68) in the low galectin-3 group (LGAL). Ventricular arrhythmic events were more frequent in HGAL than in LGAL, including non-sustained ventricular tachycardia (VTnon), sustained-VT (VTs), and ventricular fibrillation (VF) (p < 0.0001, p = 0.002, and p = 0.026, respectively). There were no statistically significant differences between HGAL and LGAL in terms of LV strain measurements. Galectin-3 level was positively significantly correlated with total arrhythmic events (r = 0.58, p < 0.001), but no correlation was found between galectin-3 and LV global longitudinal strain (r = 0.15, p = 0.16). Galectin-3 was an independent predictor of total ventricular arrhythmic events in HF patients (p < 0.0001). Conclusion VTnon, VTs, and VF events were higher in HGAL compared to LGAL. Galectin-3 was an independent predictor of total ventricular arrhythmic events in HF patients and might be used to detect high-risk HF patients for arrhythmic events.

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.

High Intratumoral Galectin-1 Is Associated with Adverse Outcome in ALK-Negative, CD30-Positive Peripheral T-Cell Lymphomas

Galectin-1 (Gal-1) has been associated with prognosis in several cancers including lymphomas. CD30-dependent cell signaling mediated by Gal-1 has been proposed in CD30-positive lymphomas and cell lines. Still, Gal-1 expression has not been systematically assessed as a possible prognosticator in nodal peripheral T-cell lymphomas (PTCL).Tissue micro arrays with pre-therapeutic tumor specimens from 169 patients with nodal PTCL (n=29 AITL, n=37 ALK-negative ALCL, n=14 ALK-positive ALCL, and n=83 PTCL-NOS) were assessed for intratumoral Gal-1 expression by immunohistochemistry and quantified using digital image analysis. For outcome analysis Gal-1 expression in tumors was categorized in two groups i.e. i) the quartile of patients with highest expression values (Gal-1 high) and ii) the lower three quartiles taken as one group (Gal-1 low). Overall survival (OS) in high and low Gal-1 groups was compared in the entire cohort and in CD30-positive subsets of PTCL.Gal-1 stains were evaluable in 163 cases (96%). The Gal-1 expression level was significantly different between PTCL subtypes (P<0.001) with ALK-positive and ALK-negative ALCL having the highest levels. Moreover, CD30-positive PTCLs showed higher expression compared with CD30-negative ones (P=0.001). No significant difference in OS according to Gal-1 expression was seen in the PTCL cohort as a whole or in the CD30-positive subgroup when including ALK-positive ALCL. Due to the superior survival and very few events among ALK-positive ALCL patients (P<0.001), a CD30-positive cohort without ALK-positive ALCL was analyzed separately. This cohort consisted of ALK-negative ALCL (n=37), PTCL-NOS (n=5), and AITL (n=1). Within this cohort, patients with ‘Gal-1 high’ had significantly poorer outcome (5 yrs OS 10%, 95% confidence interval (CI): 0.1-36) than their ‘Gal-1 low’ counterparts (5 yrs OS 48%, 95%CI: 30-64, P=0.025). Risk factors were evenly distributed between the groups. In univariate analyses age≤60, normal LDH, and performance score <2 correlated with superior survival, whereas high Gal-1 expression significantly predicted adverse outcome at both univariate (HR 2.4, 95%CI: 1,1-5.5, P=0.030) and multivariate level (HR 2.9, 95%CI: 1.1-7.8, P=0.027). We conclude that high intratumoral Gal-1 expression correlates with inferior survival in nodal ALK-negative, CD30-positive PTCL patients. Disclosuresd'Amore:Nordic Nanovector: Other: Advisory Board; Sanofi: Research Funding; Les Laboratoires Servier: Honoraria, Other: Advisory Board; Takeda Pharma: Honoraria, Other: Advisory Board, Research Funding.

Galectin-1 Expression Is Associated with the Response and Survival Following Preoperative Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

Simple SummaryGalectin-1 has been found to be involved in therapeutic resistance in a variety of cancers. However, the prognostic significance of galectin-1 expression in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with chemoradiotherapy remains unknown. Immunohistochemically, we observed that galectin-1 overexpression in pretreatment biopsied specimens was significantly associated with a lower pathological complete response rate, worse overall survival and disease-free survival in 93 patients with locally advanced ESCC receiving preoperative chemoradiotherapy. Our findings suggest that galectin-1 may be a potential therapeutic target for patients with ESCC treated with preoperative chemoradiotherapy.The galectin-1 has been found to be involved in poor outcomes after treatment of a variety of cancers. To the best of our knowledge, however, the significance of galectin-1 expression in the sensitivity to chemoradiotherapy (CCRT) of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. Expression levels of galectin-1 were evaluated by immunohistochemistry and correlated with the treatment outcome in 93 patients with locally advanced ESCC who received preoperative CCRT between 1999 and 2012. Galectin-1 expression was significantly associated with the pathological complete response (pCR). The pCR rates were 36.1% and 13.0% (p = 0.01) in patients with low and high galectin-1 expression, respectively. Univariate analyses revealed that galectin-1 overexpression, clinical 7th American Joint Committee on Cancer (AJCC) stage III and a positive surgical margin were significant factors of worse overall survival and disease-free survival. In multivariate analyses, galectin-1 overexpression and a positive surgical margin represented the independent adverse prognosticators. Therefore, galectin-1 expression both affects the pCR and survival in patients with locally advanced ESCC receiving preoperative CCRT. Our results suggest that galectin-1 may be a potentially therapeutic target for patients with ESCC treated with preoperative CCRT.

Role of sCD40L in the prediction of super-response to cardiac resynchronization therapy.

The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor a, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV = 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p?=?0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p?<?0.0001) and lateral (0 vs. 18%, p?=?0.03), inferior (4 vs. 33%, p?=?0.01) and posterior infarction (0 vs. 22%, p?=?0.01); absence of mitral regurgitation (47% vs. 22%, p?=?0.04), wider QRS width (157.7?±?22.9 vs. 140.8?±?19.2ms, p?=?0.01), higher concentrations of sCD40L (6.9?±?5.1 vs. 4.4?±?3.3 ng/mL, p?=?0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p?=?0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correla-tion with SR (r?=?0.39, p?=?0.02) and with the reduction of LVESV (r?=?0.44, p?=?0.02). sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.

Galectin-3/adiponectin as a new biological indicator for assessing the risk of type 2 diabetes: a cross-sectional study in a community population.

Objective: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance.Methods: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models.Results: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21–5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models.Conclusions: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.

Galectin-3 Binding Protein, Depression, and Younger Age Were Independently Associated With Alexithymia in Adult Patients With Type 1 Diabetes.

Aims: Alexithymia has been linked to cardiovascular disease. The aim was to explore whether the immuno-inflammatory variables galectin-3 binding protein (Gal3BP), soluble (s)CD163 and galectin-3 were independently associated with alexithymia, while controlling for known risk factors for cardiovascular disease, such as depression, anxiety, impaired glycemic control, obesity, smoking, and physical inactivity in patients with type 1 diabetes (T1D).Methods: Cross-sectional design. The participants were consecutively recruited from one diabetes out-patient clinic. Alexithymia, depression and anxiety were assessed by self-report instruments. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic health records. High Gal3BP was defined as ≥3.3 μg/ml, high sCD163 as ≥0.6 μg/ml, high galectin-3 as ≥2.6 ng/ml, impaired glycemic control as HbA1c >70 mmol/mol (>8.6%) and abdominal obesity as waist circumference ≥ 1.02 m for men and ≥ 0.88 m for women.Results: Two hundred and ninety two patients participated (men 56%, aged 18–59 years, alexithymia prevalence 15%). Patients with alexithymia had higher prevalence of depression (34 vs. 6%, p < 0.001), anxiety (61 vs. 30%, p < 0.001), high Gal3BP levels (39 vs. 17%, p = 0.004), high HbA1c levels (46 vs. 24%, p = 0.006), and abdominal obesity (29 vs. 15%, p = 0.045). Depression [adjusted odds ratio (AOR) 6.5, p < 0.001], high Gal3BP levels (AOR 2.4, p = 0.035), and age (AOR 0.96, p = 0.027) were independently associated with alexithymia. Abdominal obesity (AOR 4.0, p < 0.001), high Gal3BP levels (AOR 2.8, p = 0.002), and depression (AOR 2.9, p = 0.014) were associated with high HbA1c. Abdominal obesity and anxiety were associated [Crude odds ratio (COR) 2.4, p = 0.006].Conclusions: T1D patients with alexithymia had higher prevalence of high Gal3BP levels, depression, impaired glycemic control, anxiety, and abdominal obesity, which are known risk factors for cardiovascular disease. Only high Gal3BP levels, depression, and younger age were independently associated with alexithymia in adult patients with T1D.

The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer.

Background The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. Methods The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. Results The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p<0.0001). The patients with rs4644 CA/CC (p<0.0001 and p<0.0001) and rs4652 AA/AC (p=0.001 and p<0.0001) genotypes had higher serum galectin-3 levels than their corresponding controls. Serum galectin-3 levels increased in the presence of vascular invasion in patients with both rs4644 AC (p=0.03) and rs4652 AC (p=0.019) genotypes. The receiver operating characteristic curve suggested serum galectin-3 level as a strong predictive marker for the patient group with a cut-off value of 17.089 ng/mL (area under the curve: 0.910±0.04; 95% confidence interval: 0.832-0.988; p<0.001). Univariate analysis revealed the association of lower serum galectin-3 levels with better survival (p=0.048). Multivariate survival analysis showed that only high serum galectin-3 levels tended to be related to survival of the patients (hazard ratio: 5.106; 95% confidence interval: 0.956-27.267; p=0.056). Conclusion The presence of galectin-3 gene variants may lead to histopathological differences among patients with non-small cell lung cancer. Serum galectin-3 level may be a valuable diagnostic biomarker and be associated with survival of these patients.

Myeloma-Secreted Galectin-1 Potently Interacts with CD304 on Monocytic Myeloid-Derived Suppressor Cells.

Progression of multiple myeloma is regulated by factors intrinsic to the clonal plasma cells (PC) and by the immune effector cells in the tumor microenvironment. In this study, we investigated the interaction between CD304 expression on myeloid-derived suppressor cells (MDSC) and galectin-1 from malignant PCs in the context of autologous stem cell transplantation (ASCT) for multiple myeloma. Using high-throughput screening, CD304 expression on circulating monocytic MDSCs (M-MDSC; CD14+HLA-DRlow/-) was compared before and after ASCT. There was a significantly higher M-MDSC expression of CD304 before ASCT and a clear correlation between circulating pre-ASCT M-MDSC frequency and serum galectin-1 concentration. Treatment of pre-ASCT M-MDSCs, but not post-ASCT M-MDSCs, with galectin-1 in vitro expanded the M-MDSC population and increased expression of CD304. High galectin-1 expression by malignant PCs was associated with poor clinical outcomes. M-MDSC development and expression of CD304 were differentially induced when healthy donor peripheral blood mononuclear cells were cultured with the human multiple myeloma cell lines RPMI-8226 and JJN3, which express high and low galectin-1, respectively. Inhibition of galectin-1 reduced M-MDSC proliferation induced by RPMI-8226 cells but not by JJN3 cells, and blockade of CD304 reduced M-MDSC migration induced by RPMI-8226 cells but not by JJN3 cells. In addition, blockade of CD304 reversed suppression of the in vitro cytotoxic effect of melphalan by pre-ASCT M-MDSCs. Our data demonstrate that multiple myeloma-derived galectin-1 could mediate the tumor-promoting effect of M-MDSCs through its interaction with CD304 on M-MDSCs and contribute to multiple myeloma progression after ASCT.See related Spotlight on p. 488.

Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study

BackgroundLow levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK.MethodsCross-sectional design. T1DM patients (n = 283, men 56%, age18–59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications.ResultsFor 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93 and 68% (p = 0.003) and for high galectin-3: 34 and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005).Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression.CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK.ConclusionsLower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.

Abstract 13198: Immunohematologic Failure Identifies Fibrotic Phenotype in Heart Failure With Preserved Ejection Fraction

Background: We have shown that immunohematologic failure (IHF: lymphopenia (absolute lymphocyte count (ALC)&lt;1.5 x10 3 /μL) and anisocytosis (red cell distribution width, RDW &gt; 14.5%)) is associated with risk of heart failure. Lymphopenic patients have elevated numbers of regulatory T cells with profibrotic phenotype. Hypothesis: We hypothesized that IHF is associated with fibrosis in HFpEF. Methods: We investigated the association between ALC, RDW, and IHF with markers of fibrosis (galectin-3 and Corboxy-Terminal Telopeptide of Collagen Type I [CITP]) in patients enrolled in RELAX trial of HFpEF (Clinicaltrials.gov NCT00763867) using linear regression, and adjusting for age, sex, race, eGFR, BMI and diabetes status. Results: A total of 122 patients with both ALC and RDW were included. There was a modest correlation between ALC and RDW (Spearman’s rho=-0.22, P=0.017). Both ALC and RDW were significantly associated with galectin 3 and CITP (figure). A total of 33 (27%) patients had IHF. Patients with IHF had lower GFR (62±25 vs 53 ± 21 ml/min/1.73 m 2 , P&lt;0.001), lower peak VO2 (12.5±2.8 vs 11.0 ± 3.0 ml/kg/min, P=0.007), lower exercise capacity (78 ± 26 vs 64 ± 35 watts, P=0.018), higher NT-proBNP (900±1152 vs 1615 ± 1247 pg/mL, P=0.004), galectin-3 (13.3 ± 4.1 vs 17.7 ± 5.8, P&lt;0.001 ng/mL) and CITP (6.1 ± 3.5 vs 11.0 ± 5.7 μg/L, P&lt;0.001) but no difference in age, sex, race, CRP or diabetes status. After multiple adjustments, IHF was associated with higher galectin-3 levels (P=0.01) and CITP (P&lt;0.001). Conclusions: Immunohematologic failure is common in HFpEF and is associated with fibrotic phenotype. The mechanisms linking IHF and fibrosis need to be elucidated in future studies.

Combining Pulse Wave Velocity With Galectin-3 to Predict Mortality and Cerebrovascular and Cardiovascular Events in Hemodialysis Patients.

Background: Cerebrovascular and cardiovascular diseases contribute substantially to the mortality of end-stage renal disease patients. We sought to combine pulse wave velocity (PWV) with galectin-3 to predict the mortality and cerebrovascular and cardiovascular events in hemodialysis patients.Methods and Results: End-stage renal disease patients who underwent stable hemodialysis were screened for inclusion. Patients with preexisting cardiovascular and cerebrovascular diseases were excluded. The primary endpoint was a composite of all-cause mortality and major adverse cerebrovascular and cardiovascular events. Receiver operating characteristic curve analysis was used to determine the optimal cutoffs to dichotomize PWV and galectin-3. The study population was then stratified into four groups based on these cutoffs. Both univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio and 95% confidence interval (CI) for clinical factors. Model performance was compared among models with or without PWV and galectin-3. A total of 284 patients were enrolled. During a median follow-up of 31 months, 57 patients (20.1%) reached the primary endpoint. The optimal cutoffs for PWV and galectin-3 were 7.9 m/s and 30.5 ng/ml, respectively. In the multivariable regression analysis, the high PWV–high galectin-3 group was associated with a 3-fold increased risk of all-cause mortality and major adverse cerebrovascular and cardiovascular events (hazard ratio = 3.19, 95% CI: 1.05–9.66, p = 0.04) compared with the low PWV–low galectin-3 group. The combination of PWV and galectin-3 was associated with improved model discrimination, calibration, and reclassification.Conclusions: The combination of PWV and galectin-3 can be used to predict mortality and cerebral and cardiovascular complications in hemodialysis patients.

Higher galectin-3 levels are independently associated with lower anxiety in patients with risk factors for heart failure

BackgroundGalectin-3 promotes the proliferation of neural progenitor cells and is engaged in cell-cell adhesion, cell-matrix interactions, and macrophage activation. In addition, in patients with heart failure this carbohydrate-binding protein is a known prognostic marker for cardiovascular mortality. However, its association with psychological variables has not been investigated so far.MethodsUsing data from the multicenter, observational Diast-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) trial, we studied in participants with cardiovascular risk factors (n = 1260, age 66.7 ± 8.0 years, males 51%, left ventricular ejection fraction 60.0 ± 8.1%) the relationship between serum concentrations of galectin-3 and anxiety. Galectin-3 levels were measured by means of a sandwich enzyme-linked immunosorbent assay, and anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS).ResultsIn univariate analysis, there was a weak but significant inverse correlation between galectin-3 and HADS anxiety (rho = − 0.076; p = 0.008). Linear regression models adjusted for sex, age, body-mass index, estimated glomerular filtration rate, left ventricular ejection fraction, 6-min walking distance, the 36-item Short-Form Health Survey (SF-36) subscale physical functioning, and known biomarkers for heart failure confirmed that serum galectin-3 significantly and independently predicted self-rated anxiety (B = -2.413; 95%CI = -2.413–-4.422; p = 0.019).ConclusionIn patients with cardiovascular risk factors, serum concentrations of galectin-3 showed an inverse association with anxiety, which was independent of both the severity of physical impairment and established risk factors for the progression of heart failure.

Prognostic value of serum aquaporin-1, aquaporin-3 and galectin-3 for young patients with colon cancer

This study aimed to investigate the long-term prognosis value of serum galectin-3, aquaporin (AQP)-1 and AQP-3 in young patients with colon cancer. A total of 100 young patients with colon cancer, 100 cases of benign colon and 100 healthy people were collected. All colon cancer patients were followed up for 42 months. Compared with the benign lesion group and the control group, preoperative serum galectin-3, AQP-1 and AQP-3 concentrations were significantly increased in patients with colon cancer (P < 0.05). The immunohistochemistry scores of galectin-3, AQP-1 and AQP-3 in colon cancer patients were positively correlated with serum galectin-3, AQP-1 and AQP-3 concentrations (P < 0.05). Serum galectin-3, AQP-1 and AQP-3 concentrations were positively correlated with TNM staging (galectin-3: rPearson = 0.502, P < 0.001; AQP-1: rPearson = 0.415, P < 0.001; AQP-3: rPearson = 0.454, P < 0.001) and differentiation (galectin-3: rPearson = 0.377, P = 0.004; AQP-1: rPearson = 0.411, P = 0.001; AQP-3: rPearson = 0.483, P < 0.001). Receiver operator characteristic curve (ROC) analysis showed that the area under ROC curve (AUC) of the combination of galectin-3, AQP-1 and AQP-3 in distinguishing colon cancer was 0.907. The sensitivity in the parallel mode was 87.6%, and the specificity in the serial mode was 98.2%. Compared with the low galectin-3 group, low AQP-1 group and low AQP-3 group, the survival time of patients in the high galectin-3 group (χ2 = 13.929, P < 0.001), high AQP-1 group (χ2 = 10.157, P = 0.001) and high AQP-3 group (χ2 = 4.364, P = 0.037) were significantly shortened. Galectin-3 combined with AQP-1 and AQP-3 had important value in the identification of young patients with colon cancer and was of great value in evaluating long-term prognosis.

Galectin-3 levels and the prediction of atrial high-rate episodes in patients with cardiac resynchronization therapy

Galectin-3 is an inflammation biomarker associated with atrial remodeling which plays a role in the development of atrial fibrillation (AF). Atrial high-rate episode (AHRE) is related to development of clinically...

Galectin-3, N-terminal Propeptides of Type I and III Procollagen in Patients with Atrial Fibrillation and Metabolic Syndrome.

The aim of this study was to determine the concentration of galectin-3, PINP and PIIINP in patients with metabolic syndrome (MS) and atrial fibrillation (AF) with an assessment of the relationship with severity of left atrium fibrosis. A total of 480 subjects were included in the case-control study: MS patients (n = 337), 176 of whom had AF, 72 patients with AF without MS and 71 healthy subjects. Galectin-3, PINP and PIIINP blood concentrations and metabolic parameters were compared with the severity of left atrium fibrosis, measured by CARTO3. Galectin-3 in AF and MS patients is higher than in MS without AF and in healthy subjects (10.3 (4.8–15.4), 5.1 (4.3–8.8), 3.2 (2.4–4.2) ng/mL, p < 0.0001). Galectin-3 serum concentration in AF patients with MS is higher than in patients without MS: 10.3 (4.8–15.4), 6.8 (5.2–8.1) ng/mL, p = 0.0001. PINP and PIIINP concentration were higher in patients with AF and MS than in MS without AF: 3499.1 (2299.2–4567.3), 2130.9 (1425.3–2861.8) pg/mL, p < 0.0001, 94.9 (64.8–123.5), 57.6 (40.5–86.9) ng/mL, p < 0.0001. Galectin-3 correlates with PINP (r = 0.496, p < 0.001) and PIIINP concentration (r = 0.451, p < 0.0001). The correlation between galectin-3, PINP and the severity of left atrium fibrosis was found (r = 0.410, p < 0.001; r = 0.623, p < 0.001). Galectin-3 higher than 12.6 ng/mL increased the risk of AF more than five-fold. High galectin-3, PINP and PIIINP concentrations were associated with heart remodeling in MS patients and increased the risk of AF.

Sequence-Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin-3 and Delay Wound Healing of a Galectin-3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay.

Within this work, a new class of sequence-defined heteromultivalent glycomacromolecules bearing lactose residues and nonglycosidic motifs for probing glycoconjugate recognition in carbohydrate recognition domain (CRD) of galectin-3 is presented. Galectins, a family of β-galactoside-binding proteins, are known to play crucial roles in different signaling pathways involved in tumor biology. Thus, research has focused on the design and synthesis of galectin-targeting ligands for use as diagnostic markers or potential therapeutics. Heteromultivalent precision glycomacromolecules have the potential to serve as ligands for galectins. In this work, multivalency and the introduction of nonglycosidic motifs bearing either neutral, amine, or sulfonated/sulfated groups are used to better understand binding in the galectin-3 CRD. Enzyme-linked immunosorbent assays and surface plasmon resonance studies are performed, revealing a positive impact of the sulfonated/sulfated nonglycosidic motifs on galectin-3 binding but not on galectin-1 binding. Selected compounds are then tested with galectin-3 positive MCF 7 breast cancer cells using an in vitro would scratch assay. Preliminary results demonstrate a differential biological effect on MCF 7 cells with high galectin-3 expression in comparison to an HEK 293 control with low galectin-3 expression, indicating the potential for sulfonated/sulfated heteromultivalent glycomacromolecules to serve as preferential ligands for galectin-3 targeting.