Elevated Gal-3 Levels Research Articles

The Predictive Value of Circulating Gal-3 for New Stroke Events in Paroxysmal Atrial Fibrillation Patients Despite Oral Anticoagulation Medications.

CHA2DS2-VASc is used to assess the risk of stroke in patients with atrial fibrillation (AF) and guide anticoagulant treatment decisions, but it has limitations in accurately predicting stroke risk in individual patients. The objective of this study is to conduct a cohort study by assessing preoperative levels of Gal-3 in paroxysmal AF patients, aiming to observe its correlation with the subsequent incidence of stroke events. This study enrolled 197 patients with nonvalvular paroxysmal AF. Blood samples were taken to test Gal-3 levels. All patients were followed up for 4 years after admission. Compared to the nonstroke cases, serum levels of Gal-3 were markedly elevated in stroke cases (7.08 [IQR, 4.60-10.96] vs. 17.34 [IQR, 8.28-20.31], p < 0.001). Gal-3 yields a superior AUC (0.748, with a 95%CI of 0.681-0.807) compared to other classical stroke indices, such as BNP, CHA2DS2-Vas score, and TNI. Remarkably, the Gal-3 index exhibited a superior predictive capacity, yielding a significant incremental predictive value that surpassed the conventional risk factors (CHA2DS2-VASc score) for stroke events, as evidenced by an IDI of 16.4% (p < 0.001) and an NRI of 34.7% (p = 0.002). The presence of Gal-3 is an independent risk factor for stroke in patients with AF. Elevated levels of Gal-3 have the potential to serve as a valuable biomarker for identifying incident strokes in AF patients. Furthermore, incorporating the assessment of Gal-3 levels into the conventional CHA2DS2-VASc score could significantly enhance its predictive accuracy for stroke in AF patients.

Serum Galectin-3 and IL-6 as Inflammatory Markers in Bipolar Disorder: Insights from Manic and Euthymic Episodes

Objectives: This study aimed to assess serum Galectin-3 (Gal-3) and IL-6 levels, along with other inflammatory markers, in type-1 bipolar disorder (BD) patients and explore their relationship with clinical features, metabolic parameters, and symptom severity. Background: The study included 38 manic, 35 euthymic BD patients, and 40 healthy controls. Sociodemographic data, such as age, gender, alcohol and smoking habits, and body mass index (BMI), were recorded. Methods: The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) were administered to patients. Biochemical measurements included Gal-3, IL-6, CRP, neutrophil, lymphocyte, platelet counts, and inflammatory indices like NLR, PLR, SII, and SIRI. Results: Gal-3 levels significantly differed among the groups (F = 52.251, p &lt; 0.001), with the highest levels in euthymic patients. IL-6 levels were elevated in both manic and euthymic patients compared to controls (F = 7.379, p = 0.001). Manic patients had significantly higher levels of neutrophils, monocytes, CRP, NLR, PLR, SII, and SIRI. A positive correlation was found between Gal-3 levels, the total number of episodes, and YMRS scores in manic patients. In euthymic patients, Gal-3 levels correlated positively with disease duration and episode count. Conclusions: Elevated Gal-3 levels, particularly in the euthymic phase, may serve as a biomarker for BD and indicate ongoing inflammation. These findings suggest Gal-3 could help identify BD and differentiate the euthymic phase.

Effect of galectin-3, IL-1, IL-6 and TNF-alpha on disease prognosis and mortality in COVID-19 patients.

COVID-19 is a significant cause of morbidity and mortality. It is crucial to identify biomarkers that can aid in predicting patients' prognosis and mortality. This study evaluated the relationship between galectin-3 (Gal-3), interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels and the prognosis and mortality of COVID-19 patients. The study included 69 COVID-19 patients (32 outpatients, 37 inpatients) and 19 healthy controls. Gal-3, IL-1, IL-6, and TNF-α levels in serum samples were measured using an ELISA test. In a comparison between the patient and healthy control groups, it was observed that the patient group had significantly higher levels of Gal-3, IL-6, and TNF-α. Comparison between the outpatient and inpatient groups revealed that the hospitalized patient group had significantly higher levels of IL-6 and TNF-α, while the Gal-3 levels were lower in this group. In the analysis of subgroups to assess disease severity, critical COVID-19 patients exhibited elevated levels of Gal-3 and IL-6 compared to those with severe COVID-19. Moreover, Gal-3 and IL-6 were identified as having predictive value for mortality in hospitalized patients, while both IL-6 and TNF-α demonstrated diagnostic accuracy across all patient groups. The study results indicate that the levels of IL-6 TNF-α play a crucial role in determining the hospitalization and mortality of COVID-19 patients. Additionally, it was observed that Gal-3 and IL-6 levels can be utilized to assess the severity of the disease and predict mortality in patients who require hospitalization.

Prognosis value of galectin-3 in patients with dilated cardiomyopathy: a meta-analysis.

Accurate prediction and assessment of myocardial fibrosis (MF) and adverse cardiovascular events (MACEs) are crucial in patients with dilated cardiomyopathy (DCM). Several studies indicate that galectin-3 (gal-3) as a promising prognostic predictor in patients with DCM. A comprehensive search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant studies up to August 2023. The hazard ratios (HRs) of gal-3 for MACEs in DCM patients, and for MACEs in LGE(+) versus LGE(-) groups, were evaluated. Statistical analysis was performed using STATA SE 14.0 software. Seven studies, encompassing 945 patients, met the eligibility criteria. In DCM patients, abnormally elevated gal-3 levels were indicative of an increased MACEs risk (HR = 1.10, 95% CI [1.00-1.21], I2 = 65.7%, p=0.008). Compared with the LGE(-) group, the level of gal-3 in LGE(+) group was higher (HR = 1.12, 95% CI [1.05-1.19], I2 = 31.4%, p=0.233), and the combination of gal-3 and LGE significantly improved the prediction of MACEs. Sensitivity analysis confirmed the robustness of all results. This study's findings suggest that elevated gal-3 levels significantly correlate with increased MACE risk in DCM, highlighting its potential as a biomarker. However, significant heterogeneity among studies necessitates further research to ascertain gal-3's predictive and diagnostic value in DCM prognosis, particularly in conjunction with LGE. CRD42023471199.

Galectin-3 and its correlation with carotid ultrasound in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease resulting in disability as well as joint damage. Early diagnosis and treatment are crucial for improving outcomes. RA patients have a twofold elevated risk of cardiovascular disease (CVD) development compared to the general population. Carotid ultrasound is a noninvasive imaging modality that can detect early signs of atherosclerosis and plaque buildup in the carotid arteries, which are strongly associated with CVD risk. Galectin-3 (Gal-3), a protein involved in inflammation and fibrosis, is suggested as one of the potential RA markers. Despite the growing interest in galectin-3 as a biomarker for CVD, few studies have investigated its role in RA patients. To our knowledge, only two studies have examined the correlation between galectin-3 and CVD in RA patients, and they have yielded conflicting results. This study aimed to determine the serum level of Gal-3 as well as its correlation with carotid ultrasound assessment for cardiovascular involvement in RA patients.ResultsRA cases demonstrated substantially elevated Gal-3 levels than controls (P < 0.001), and a 3.38 pg/mL cut-off value was proven to be an excellent predictor of RA diagnosis (AUC, 0.98). Gal-3 levels were proven to be positively associated with DAS-28, Larsen score, and carotid intima-media thickness (CIMT) (P-value 0.006, 0.026, < 0.001, respectively). A positive association was also detected between right (RT) and left (LT) CIMT and disease duration (P-values of 0.040 and 0.042, respectively).ConclusionsGal-3 is a biomarker for RA that is not only associated with activity and severity of the disease but it is also related to the chronicity of the disease and is a predictor of cardiovascular comorbidity.

Galectin-3 regulates skeletal muscle loss via TGFβ1-Smad2/3 signaling activation in mice

IntroductionEndogenous glucocorticoids (GCs) played a pivotal role in the pathogenesis of skeletal muscle loss. However, to date, the underlying molecular mechanisms underlying are not yet fully understood. Galectin-3 (Gal-3) is a member of a beta-galactoside-binding animal lectins, consistently associated with inflammation and fibrosis in the pathogenesis of various disease states. The present study aimed to explore the role of Gal-3 in GC-induced skeletal muscle loss.Material and methodsMyogenic differentiation capacity was detected after in vitro Gal-3 knockdown (KD) or in vivo administration of Gal-3 inhibitor. The activation of transforming growth factor type beta 1 (TGFβ1) and Smad2/3 signaling pathways was determined by western blot, co-immunoprecipitation, and immunofluorescence.ResultsGal-3 was up-regulated during dexamethasone (Dex) administration in mice. In the established GC-induced muscle loss model, Gal-3 inhibition recovered grip strength and muscle mass. In vitro, Gal-3 KD promoted the myogenic differentiation capacity of C2C12 myoblasts, and prevented the reduction of fully differentiated myotubes. Gal-3 results in overexpression of TGFβ1 and TGFβR-I, which affects Smad2, 3 phosphorylation and subsequently mediates skeletal muscle reduction by activating the Smad2/3 signaling pathways.ConclusionsThe present study demonstrated that Dex elevated Gal-3 levels in skeletal muscle. Gal-3 facilitates the activation of TGFβ1-Smad2/3 signaling pathways in myoblasts, and contributes to myogenesis inhibition and skeletal muscle loss. This study raises awareness about the follow-up of patients receiving GC therapy. Further, inhibition of Gal-3 provides a possible therapeutic strategy for skeletal muscle loss.

Abstract P086: Metabolic Risk, Galectin-3 And Heart Failure: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Diabetes and metabolic syndrome (MetS) confer an increased risk of heart failure (HF) through poorly understood mechanisms. Galectin-3 (Gal-3) is a marker of fibrosis linked to greater HF risk. The inter-relationships among diabetes, MetS and Gal-3, and related implications for HF risk, are not well understood. Hypothesis: Diabetes and MetS are associated with elevated Gal-3, and high Gal-3 indicates greater HF risk among those with diabetes or MetS. Methods: We included 8,445 participants (mean age 63, 59% male, 21% Black) at ARIC Visit 4 (1996-1999) without baseline HF. We categorized participants by metabolic risk (no diabetes/no MetS; MetS only; diabetes with or without MetS), and Gal-3 levels (gender-specific quartiles). We assessed the associations of metabolic risk categories with high Gal-3 (≥75 th percentile) using logistic regression. We used Cox regression to evaluate associations of cross-categories of metabolic risk group and Gal-3 quartiles with incident HF. Results: In cross-sectional analyses, those with MetS were more likely to have elevated Gal-3 levels than those with no diabetes or MetS (OR 1.29, 95%CI 1.13-1.47). The additional presence of diabetes did not change the likelihood of elevated Gal-3 (OR 1.29, 95%CI 1.08-1.55). Over 20.5 years of follow-up, there were 1,611 HF events. Higher Gal-3 was associated with higher HF risk in each metabolic risk group, and higher metabolic risk group was associated with greater HF risk in each Gal-3 quartile. There was no interaction between Gal-3 and metabolic risk group on HF risk ( P =0.15). The combination of diabetes &amp;MetS and high Gal-3 was associated with an almost 5-fold higher risk of incident HF (HR 4.93; 95% CI: 3.77 - 6.44) than the combination of no diabetes/MetS and low Gal-3 (first quartile) ( Table ). Conclusions: MetS was associated with higher levels of Gal-3. Metabolic risk group and Gal-3 provided powerful complementary prognostic information regarding HF risk. Fibrosis likely plays a role in the development of HF linked to metabolic risk.

Possible value of galectin-3 on follow-up of cardiac remodeling during glucocorticoid treatment.

Glucocorticoids are among the most prescribed drugs globally due to their potent anti-inflammatory and immunosuppressive properties. Although they have positive effects on the treatment of various disease states; long-term administration is associated with high blood pressure, insulin resistance, and susceptibility to type 2 diabetes. The heart attempts to cope with increased blood pressure and a decrease in glucose utilization by developing pathological cardiac remodeling. However, in this process, cardiac fibrosis formation and deterioration in heart structure and functions occur. Galectin-3, a member of the β-galactoside binding lectins, is consistently associated with inflammation and fibrosis in the pathogenesis of various disease states including insulin resistance and heart failure. Galectin-3 expression is markedly increased in activated macrophages and a subset of activated fibroblasts and vascular cells. Also, failing and remodeling myocardium show increased Gal-3 expression and elevated Gal-3 levels are related to heart failure severity and prognosis. Furthermore, Gal-3-related pathways are recently suggested as therapeutic targets both pharmacologically and genetically to increase insulin sensitivity in vivo. The objective of this review is to provide a summary of our current understanding of the role of glucocorticoid-associated insulin resistance, which is important for some cardiac events, and the potential role of galectin in this pathophysiological process.

Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension

We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation.

Elevated galectin-3 in women with gestational diabetes mellitus, a new surrogate for cardiovascular disease in women.

BackgroundGestational diabetes mellitus (GDM) is associated with future cardiovascular morbidity and recognized as a women-specific risk factor for cardiovascular disease. The mechanisms for this association are not well established. Therefore, we aimed to evaluate the cardiovascular-related biomarkers, galectin-3 (Gal-3) and protein convertase subtilisin/kexin (PCSK) type 9, in women with GDM.MethodsBlood samples were drawn in the third trimester from 31 women diagnosed with GDM and from 35 women with normal pregnancies. Blood levels of Gal-3 and PCSK-9 were measured using a quantitative sandwich enzyme immunoassay. In addition, we measured Gal-3 levels in 24 pregnant women in the first trimester who later developed GDM and in 36 healthy controls. Continuous variables were compared using student’s t-test and categorical variables by chi-square/fisher's exact tests.ResultsWe found increased levels of Gal-3 in women diagnosed with GDM compared to women without GDM (124.6±32% versus control; pv = 0.001). Furthermore, we demonstrated elevated levels of Gal-3 during the first trimester among women who later developed GDM compared with women who did not develop any gestational morbidity (125.7±32% versus control; pv = 0.004). Third-trimester levels of PCSK-9 did not differ between women with and without GDM (560±45ng/mL versus 553±33ng/mL; pv = 0.4).ConclusionsThe results suggest a possible mechanism that may link GDM to the future increased cardiovascular risk in these patients. Additionally, increased Gal-3 levels during the first trimester may suggest a new early predictor for GDM.

Galectin-3 as a Predictor of Long-term Survival After Isolated Coronary Artery Bypass Grafting Surgery

Galectin-3 (Gal-3) is a well-established biomarker of adverse clinical outcomes, but its prognostic value for long-term survival after cardiac surgery is not well understood. Elevated levels of Gal-3 have been found to be remarkably associated with higher risk of death in both acute decompensated and chronic heart failure populations. Its prognostic value for long-term survival after cardiac surgery is not known. A sample of patients contributing to the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry from 2004 to 2007 were enrolled in a prospective biomarker cohort (N= 1690). Preoperative Gal-3 levels were measured and categorized by quartile. We used Kaplan-Meier survival analysis and Cox regression models, adjusting for variables in The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy probability calculator to evaluate the association between elevated Gal-3 levels and survival to 6 years. Preoperative Gal-3 levels ranged from 1.72 to 28.89 ng/mL (mean, 8.96 ng/mL; median, 8.06 ng/mL; interquartile range, 5.42-11.08 ng/mL). Crude survival decreased by increasing quartile. After adjustment, serum levels of Gal-3 in the highest quartile of the cohort were associated with significantly decreased survival compared with the lowest quartile (hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.40-3.54; P= .001). No decrease in survival was found for the middle quartiles (HR 1.36; 95% CI, 0.87-2.12; P= .177). A substantial association was found between elevated preoperative Gal-3 levels and risk of mortality after isolated coronary artery bypass grafting surgery. An assessment of the relationship between preoperative serum biomarkers and long-term survival can be used for risk stratification or estimating postsurgical prognosis.

Galectin-3 is expressed in vascular smooth muscle cells and promotes pulmonary hypertension through changes in proliferation, apoptosis, and fibrosis.

A defining characteristic of pulmonary hypertension (PH) is the extensive remodeling of pulmonary arteries (PAs), which results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. There is no cure for PH and identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis, and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMCs) is a vital objective. Galectin-3 (Gal-3) is a chimeric lectin and potent driver of many aspects of fibrosis, but its role in regulating PASMC behavior in PH remains poorly understood. Herein, we evaluated the importance of increased Gal-3 expression and signaling on PA vascular remodeling and cardiopulmonary function in experimental models of PH. Gal-3 expression was quantified by qRT-PCR, immunoblotting, and immunofluorescence imaging, and its functional role was assessed by specific Gal-3 inhibitors and CRISPR/Cas9-mediated knockout of Gal-3 in the rat. In rat models of PH, we observed increased Gal-3 expression in PASMCs, which stimulated migration and resistance to apoptosis, whereas silencing or genetic deletion reduced cellular migration and PA fibrosis and increased apoptosis. Gal-3 inhibitors attenuated and reversed PA remodeling and fibrosis, as well as hemodynamic indices in monocrotaline (MCT)-treated rats in vivo. These results were supported by genetic deletion of Gal-3 in both MCT and Sugen Hypoxia rat models. In conclusion, our results suggest that elevated Gal-3 levels contribute to inappropriate PA remodeling in PH by enhancing multiple profibrotic mechanisms. Therapeutic strategies targeting Gal-3 may be of benefit in the treatment of PH.

Emerging Role of Galectin-3 in Pulmonary Artery Hypertension

Pulmonary arterial hypertension (PAH) is multifactorial disadptive disease with poor clinical outcomes associated with increased pulmonary artery pressure resulting in primary small-to-moderate pulmonary artery remodeling. Numerous factors, including smooth muscle cell proliferation, vasospasm, vascular fibrosis and occlusion, direct vascular injury and inflammation, impaired repair of vasculature, are involved in the pathogenesis of PAH. It has been suggested that galectin-3 as a biomarker of excessive fibrosis and inflammation can be useful predictor of both severity and prognosis in patient with PAH. The short communication is reported that elevated Gal-3 levels were found in majority patients with PAH depending on clinical status and of the disease. Although elevated Gal-3 levels were associated with a higher risk of all-cause mortality, cardiovascular mortality, and right ventricle heart failure, the value of this biomarker in PAH patients at high risk stratification is uncertain and requires to be investigated in large clinical trials.

Galectin-3 levels in patients hospitalized for decompensated heart failure

Background: Galectin-3 (Gal-3) is a mediator of myocardial fibrosis involved in cardiac remodeling and a potential new prognosis marker in heart failure (HF). Aim: To measure Gal-3 at the moment of discharge in patients hospitalized for HF and its association with different variables. Material and methods: Patients hospitalized for decompensated HF from four hospitals between August 2014 and March 2015, were included. Demographic, clinical and laboratory variables were recorded at the time of admission. At discharge, a blood sample was withdrawn to measure Gal-3 and brain natriuretic propeptide (Pro-BNP). Patients were separated in two groups, according to the level of Gal-3 (using a cutoff value of 17.8 ng/mL), comparing clinical and laboratory values between groups. Results: We included 52 patients with HF aged 70 ± 17 years (42% females). Functional capacity was III to IV in 46% of patients and the ejection fraction was 34.9 ± 13.4%. Pro-BNP values at discharge were 5323 ± 8665 pg/mL. Gal-3 values were 23.8 ± 16.6 ng/mL. Sixty percent of patients had values over 17.8 ng/mL. Those with elevated Gal-3 levels were older (75 ± 16 and 62 ± 15 years respectively, p = 0.025) and were hypertensive in a higher proportion (90.5% and 57.1% respectively, p = 0.021). Conclusions: In patients hospitalized for HF, Gal-3 levels are higher in older and hypertensive subjects.

Using the galectin-3 test to predict mortality in heart failure patients: a systematic review and meta-analysis.

Galectin-3 (Gal-3) is a new biomarker for assessing prognosis of heart failure (HF) patients. This systemic review and meta-analysis aims to examine Gal-3's ability in assessing prognosis of HF patients. We searched MEDLINE and Embase up to November 2014. Test performance characteristics were summarized using forest plots and hierarchical summary receiver operating characteristic curves. The diagnostic odds ratio of Gal-3 in predicting mortality in chronic HF patients was 2.36 (95% CI: 1.71-3.26) and 2.30 (95% CI: 1.76-3.01) in acute HF patients. Elevated levels of Gal-3 are associated with mortality in both acute and chronic HF patients. However, current evidence does not support sole use of Gal-3 for prognosis evaluation of HF patients.

Abstract 47: Expression of Galectin-3 in the Myocardium and Arterial Walls of Kawasaki Disease Patients

Background: Although coronary artery aneurysms are the most significant complication of Kawasaki Disease (KD), histologic examination has revealed myocarditis and myocardial fibrosis (MF) in most cases. Galectin-3 (Gal-3) is a matricellular protein that plays a multifunctional role in inflammation, fibrosis, and cell differentiation. It is a prognostic indicator of heart failure and cardiovascular events. Gal-3 plays a role in adhesion and migration of inflammatory and fibroblastic cells. We previously reported that plasma Gal-3 levels were elevated in acute pediatric KD and adult KD with giant aneurysms (GA). We postulated that Gal-3 may be involved in both acute inflammation and convalescent fibrosis in KD. Methods: Conventional H&amp;E staining, Trichrome staining and immunohistochemical analysis for Gal-3 were performed on 1 acute stage KD subject and 10 convalescent stage KD hearts including 6 from subjects with GA and 4 from subjects without aneurysms who died of non-cardiovascular causes. Results: In the acute KD myocardium, round inflammatory cells were seen infiltrating the myocardium and positive staining for Gal-3 was noted. In the myocardium of convalescent KD with GA, widespread cardiomyocyte degeneration and necrosis with extensive bridging fibrosis were observed but inflammatory cells were not detected; spindle-shaped cells expressing Gal-3 in the cytoplasm were observed between cardiomyocytes. Myocardial fibrosis and Gal-3 expression were not observed in the myocardium of KD subjects without aneurysms. In the acute KD coronary arteries, Gal-3 positive inflammatory cells were observed in all layers, and the intima was already thickened by illness day 7. Destruction of the internal elastic lamina and intimal thickening with Gal-3-positive spindle-shaped cells were observed in coronary and systemic arteries of convalescent KD subjects. Conclusion: Gal-3 expression was related to inflammation in acute KD and tissue fibrosis in late convalescent KD with GA. Elevated levels of Gal-3 should raise concern for MF in KD patients with GA. However, in KD without aneurysms, myocardial fibrosis and Gal-3 expression were not observed; therefore myocarditis in KD patients with normal coronary arteries may improve without progression to MF.

PRE-HEART TRANSPLANT ELEVATED GALECTIN-3 LEVELS PREDICT POOR EXERCISE CAPACITY POST TRANSPLANT

Galectin (Gal) -3 is a novel biomarker which reflects cardiac remodeling and fibrosis. Elevated Gal-3 levels are associated with poor prognosis in patients with heart failure (HF). The significance of pre-heart transplant (HTx) Gal-3 levels on post-HTx outcomes is unknown. Serum Gal-3 levels were

Serum level of galectin-3 and its clinical significance in patients with chronic Keshan disease

ObjectiveKeshan disease (KD) is a fatal endemic dilated cardiomyopathy with unclear etiology and pathogenesis, and a high mortality in China. Pathologic studies confirmed that different degree of myocardial fibrosis existed in various types of KD. Myocardial fibrosis is an important contributor to the pathophysiology of left ventricular remodeling. Recently, galectin-3 (Gal-3) as a marker of cardiac fibrosis and heart failure was approved by the US FDA. The aim of this study was to evaluate the changes of serum level of Gal-3 in chronic KD (CKD) and their clinical implications. MethodsThe levels of serum Gal-3 were measured by using enzyme-linked immunosorbent assay (ELISA) in 37 CKD patients and 32 healthy controls. Echocardiography was used to determine parameter of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD). ResultsThe serum concentration of Gal-3 ([95.81±18.99] ng/ml versus [48.16±11.09] ng/ml, t=6.906, P<0.001) and LVEDD ([60.46±7.63] mm versus (42.69±10.66) mm, t=3.61, P<0.01) were significantly higher, while LVEF ([42.69±10.66]% versus [62.16±6.38]%, t=4.679, P<0.01) were significantly lower in CKD patients compared with healthy controls. A negative correlation was found between elevated Gal-3 and lower LVEF (r=−0.882, P<0.001) and a positive correlation was found between elevated Gal-3 levels and enlarged LVEDD (r=0.834, P<0.001) or higher NYHA class (r=0.854, P<0.01) in CKD patients. ConclusionSerum concentration of Gal-3 is strongly correlated with poorer left ventricular systolic function, enlarged LVEDD and higher New York Heart Association (NYHA) class, which may provide indirectly diagnostic information on myocardial fibrosis and heart function in CKD patients.

Coordinated expression of galectin‐3 and caveolin‐1 in thyroid cancer

Galectin-3 (Gal3) is the single most accurate marker for the diagnosis of differentiated thyroid cancer (DTC). Gal3 overrides the tumour suppressor activity of caveolin-1 (Cav1) and functions in concert with Cav1 to promote focal adhesion turnover and tumour cell migration and invasion. To study their coordinated role in progression of a human cancer, we investigated the expression of Gal3 and Cav1 in specimens of human benign thyroid lesions, DTC and anaplastic thyroid cancer (ATC). Gal3 and Cav1 expression is significantly associated with DTC and ATC, but not benign nodules. Essentially all Cav1-positive DTC cancers express Gal3, supporting the synergistic activity of these two proteins in DTC progression. Similarly, coordinated elevated Gal3/Cav1 expression was observed in three DTC-derived cell lines (papillary TCP1 and KTC1 and follicular FTC133) but only one (ACT1) of five ATC-derived cell lines. Using siRNA knockdown, Gal3 and Cav1 were shown to be required for RhoA GTPase activation, stabilization of focal adhesion kinase (FAK; a measure of focal adhesion signalling and turnover) and increased migration of the DTC cell lines studied, but not the ATC cell lines, including ACT1, which expresses elevated levels of Gal3 and Cav1. Co-expression of Gal3 and Cav1 in the T238 anaplastic cell line stabilized FAK-GFP in focal adhesions. Gal3 and Cav1 therefore function synergistically to promote focal adhesion signalling, migration and progression of DTC.

Galectin-3 Functions as an Adhesion Molecule to Support Eosinophil Rolling and Adhesion under Conditions of Flow

Allergic inflammation involves the mobilization and trafficking of eosinophils to sites of inflammation. Galectin-3 (Gal-3) has been shown to play a critical role in eosinophil recruitment and airway allergic inflammation in vivo. The role played by Gal-3 in human eosinophil trafficking was investigated. Eosinophils from allergic donors expressed elevated levels of Gal-3 and demonstrated significantly increased rolling and firm adhesion on immobilized VCAM-1 and, more surprisingly, on Gal-3 under conditions of flow. Inhibition studies with specific mAbs as well as lactose demonstrated that: 1) eosinophil-expressed Gal-3 mediates rolling and adhesion on VCAM-1; 2) alpha(4) integrin mediates eosinophil rolling on immobilized Gal-3; and 3) eosinophil-expressed Gal-3 interacts with immobilized Gal-3 through the carbohydrate recognition domain of Gal-3 during eosinophil trafficking. These findings were further confirmed using inflamed endothelial cells. Interestingly, Gal-3 was found to bind to alpha(4) integrin by ELISA, and the two molecules exhibited colocalized expression on the cell surface of eosinophils from allergic donors. These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.