Plasma Galectin-3 Levels Research Articles

Diagnostic value of galectin-3 in heart transplant recipients with myocardial complications

Objective : to determine the diagnostic value of galectin-3 in transplant recipients with myocardial fibrosis and acute heart transplant rejection, verified by endomyocardial biopsy. Materials and methods . The study included 124 patients with end-stage heart failure. Their ages ranged from 16 to 71 (average 48 ± 12) years, of which 106 (85%) were men and 18 (15%) were women. From 2013 to 2016, these patients underwent a heart transplant procedure at the Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation. Analysis of endomyocardial biopsy specimens was used to verify acute cellular, humoral rejection and myocardial fibrosis of the heart transplant. Severity and nature of fibrosis was evaluated using a qualitative imaging technique. Galectin-3 concentration was measured by enzyme immunoassay using Human Galectin-3 Platinum ELISA reagent kits (Bender MedSystems GmbH, Vienna, Austria). Results . In the long-term post-transplantation period, in comparison with the early post-transplantation period, the number of verified graft myocardial fibrosis increased by 88% in recipients who had acute rejection crises and by 37% in recipients who had no rejection crises. Graft myocardial fibrosis was detected more often in recipients who had acute humoral rejection than in those who had acute cell rejection (92% vs 75% of cases, respectively). Plasma galectin-3 levels in recipients with graft myocardial fibrosis was higher than in recipients without it (p = 0.05 1 year and p = 0.01 1–5 years after heart transplantation). In recipients who had acute rejection crises, the risk of developing graft myocardial fibrosis was 1.64 (RR = 1.64 ± 0.1 [95% CI 1.1–2.2]). Conclusion . Galectin-3 is a biomarker for myocardial fibrosis in acute heart transplant rejection.

Effect of Galectin 3 on Aldosterone-Associated Risk of Cardiovascular Mortality in Patients Undergoing Coronary Angiography

Recent experimental studies have suggested that galectin-3 has an interaction with aldosterone, and modifies its adverse effects. We therefore aimed to elucidate whether the relationship between plasma aldosterone concentrations (PACs) and long-term fatal cardiovascular (CV) events would depend on plasma galectin-3 levels. A total of 2,457 patients (median age: 63.5 [interquartile range (IQR) = 56.3 to 70.6] years, 30.1% women) from the LUdwigshafen RIsk and Cardiovascular Health study, with a median follow-up of 9.9 (IQR = 8.5 to 10.7) years, were included. We tested the interaction between aldosterone and galectin-3 for CV-mortality using a multivariate Cox proportional hazard model, reporting hazard ratios (HRs) with 95% confidence intervals (95%CIs). Adjustments for multiple CV risk factors as well as medication use were included. Mean PAC was 79.0 (IQR = 48.0 to 124.0) pg/ml and there were 558 (16.8%) CV deaths. There was a significant interaction between PAC and galectin-3 (p = 0.021). When stratifying patients by the median galectin-3, there was a significant association between aldosterone and CV-mortality for those above (HR per 1 standard deviation = 1.14; 95%CI [1.01 to 1.30], p = 0.023), but not below the cut-off value (HR per 1 standard deviation = 1.00; 95%CI [0.87 to 1.15], p = 0.185). In conclusion, the current study demonstrates for the first time a modifying effect of galectin-3 on the association between aldosterone and CV-mortality risk in humans. These findings indicate that galectin-3 is an intermediate between aldosterone and adverse outcomes.

Galectin-3 Identifies a Subset of Macrophages With a Potential Beneficial Role in Atherosclerosis.

Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results: We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe-/- mice. Accordingly, compared with Lgals3+/+:Apoe-/- mice, Lgals3-/-:Apoe-/- mice displayed altered plaque composition through increased macrophage:smooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3-/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-β1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12-/-:Apoe-/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12-/-:Apoe-/- mice compared with Mmp12+/+:Apoe-/- animals. This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.

Galectin-3 Is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes.

Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. Results. Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113–195) vs. 133 (105–173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81–6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07–2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04–1.42); p = 0.017 and HR 1.23 (1.05–1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. Conclusion: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

Elevated plasma galectin-3 levels and their correlation with disease activity in adult-onset Still's disease.

With galectin-3 playing an important role in inflammatory responses, elevated galectin-3 levels have been shown in patients with autoimmune diseases. However, there are limited data regarding galectin-3 expression in patients with autoinflammatory diseases such as adult-onset Still's disease (AOSD). This study aimed to investigate the extracellular galectin-3 expression and examine its association with activity parameters and disease outcome in AOSD patients. Plasma levels of galectin-3 and inflammasome downstream cytokines including interleukin (IL)-1β and IL-18 were determined by ELISA in 42 active AOSD patients and 20 healthy controls (HC). The protein levels of galectin-3 and cytokines were determined using immunoblotting. Plasma levels of galectin-3 and inflammasome downstream cytokines including IL-1β and IL-18 were significantly higher in AOSD patients (median 5.02ng/ml, interquartile range [IQR] 3.12-7.88ng/ml; 3.42pg/ml, IQR 1.48-6.70pg/ml; and 5758pg/ml, IQR 859-11,895pg/ml, respectively) compared with HC (1.86ng/ml, IQR 1.09-2.89ng/ml; 0.99pg/ml, IQR 0.62-1.35pg/ml; and 129pg/ml, IQR 71-155pg/ml, respectively, all p < 0.001). Plasma galectin-3 levels were positively correlated with clinical activity scores, inflammatory parameters values, and the levels of IL-1β and IL-18 in AOSD patients. AOSD patients with systemic pattern had significantly higher galectin-3 levels (median 6.08ng/ml, IQR 4.01-9.54ng/ml) compared with those with chronic articular pattern (3.56ng/ml, IQR 3.04-4.98ng/ml, p < 0.05). After 6-month therapy, galectin-3 levels significantly declined, paralleling the decreases in clinical activity scores and plasma levels of IL-1β and IL-18. Elevated galectin-3 levels and their positive correlation with disease activity scores, inflammatory parameter, and inflammasome downstream cytokines suggest the involvement of galectin-3 in AOSD pathogenesis.Key Points• We revealed for the first time the association of plasma galectin-3 levels with AOSD activity parameters.• We explored the link between galectin-3 levels and NLRP3-inflammasome downstream cytokines in AOSD disease.

Plasma Galectin-3 and urine proteomics predict FEV1 improvement in omalizumab-treated patients with severe allergic asthma: Results from the PROXIMA sub-study

BackgroundPatients with severe allergic asthma (SAA) when treated with omalizumab may exhibit different extent of response. Identifying biomarkers that can predict the extent of treatment effectiveness in patients can be useful in personalizing omalizumab treatment. MethodsPatients from the longitudinal phase of the PROXIMA study were selected for this ancillary study. After 12 months of omalizumab treatment, patients were categorized according to their response to treatment as: "clinical responder" (Asthma Control Questionnaire [ACQ] total score <1 at Month 12 and/or with a reduction in number of exacerbation versus the previous year); "functional responder" (an increment of ≥0.1 L in forced expiratory volume in 1 s [FEV1] at Month 12 versus baseline); and "super responder" (among clinical responders group, who also showed a functional response). Plasma galectin-3 (GAL-3) levels were quantified using a micro titer plate-based enzyme linked immunosorbent assay kit. ResultsThe Majority of patients (86.36%) in sub-study population were identified as clinical responders. Of the total patients identified as clinical responders, 64.86% were identified as super responders. A statistically significant difference in the baseline plasma GAL-3 levels between responders and non-responders was observed only in the functional responders group (P = 0.0446). Patients with plasma GAL-3 level of ≥11 ng/mL had a greater probability of being a super responder (P = 0.0118) or a functional responder (P = 0.0032). ConclusionOur findings support the use of plasma GAL-3 as a predictive marker to stratify responders and identify super responders and functional responders to omalizumab treatment in patients with severe allergic asthma using less invasive sample like plasma.

Assessment of Relationship between Galectin-3 and Biochemical Parameters in Peritoneal Dialysis Patients with Left Ventricular Hypertrophy

Introduction: Cardiovascular complications are considered as the main cause of mortality in patients with End-Stage Renal Disease (ESRD). Cardiovascular Disease (CVD) includes disorders of the Left Ventricular Hypertrophy (LVH) of the heart which is the most frequent cardiac alteration in ESRD. Galectin-3 (GAL-3), a β-galactoside-binding protein has been proposed to be a new clinical biomarker that reflects cardiac fibrosis in patients with Heart Failure (HF). Aim: To evaluate the relationship between GAL-3 and biochemical parameters in Peritoneal Dialysis (PD) patients with and without LVH. Materials and Methods: This cross-sectional study enrolled 45 patients (25 women and 20 men) with ESRD who were categorised as having CVD with (n=12) or without (n=33) LVH. Demographic, biochemical and clinical characteristics of 45 patients were analysed. The relationship of plasma GAL-3 levels was analysed with the biochemical parameters for both the groups of patients. For comparison between groups, Student unpaired t-test was used for the data of normal distribution while Mann-Whitney test was used for data of non-Gaussian distribution. Pearson’s correlation test was performed to examine various correlations. Results: Significantly high number (83.3%) of female patients were observed in ESRD with LVH. The groups did not differ significantly in their demographic, and biochemical and clinical parameters. There was significant increase in Left Ventricular End-Diastolic Diameters (LVEDD), Left Ventricular (LV) mass and LV mass index in patients with LVH as compared to the patients without LVH. The levels of GAL-3 showed slight increase (91±23.98 ng/mL) levels in LVH patients as compared to the patients without LVH (83.68±32.8 ng/mL). Exponential positive correlation between serum levels of GAL-3 and creatinine in ESRD patients without LVH (r=0.563, p=0.001). GAL-3 also showed positive correlations with urea without (r=0.563, p=0.001) as well as and uric acid (r=0.416, p=0.0178) for ESRD patients without LVH. However, GAL-3 showed no association with uric acid and urea (r=0.04487, p=0.896; r=0.2383, p=0.48) in ESRD patients with LVH. Conclusion: GAL-3 positively correlated to the biochemical parameters in ESRD patients. Patients with LVH only showed positive correlation between GAL-3 and creatinine. Moreover, GAL-3 could not be used as the biomarker because it did not correlate with established diagnostic parameter like LV mass and LV mass index. Hence, in this study GAL-3 is not a potential clinical biomarker for the progression of cardiovascular complications in ESRD patients. Overall, these data reflect the need for further investigation of GAL-3 to HF in patients with ESRD.

CLINICAL CHARACTERISTICS OF MEN AND WOMEN IN YOUNG AND MIDDLE AGE WITH ARTERIAL HYPERTENSION AT DIFFERENT GALECTIN-3 PLASMA LEVELS ACCORDING TO THE RESULT OF LINEAR REGRESSION ANALYSIS

The aim of the research was to describe the clinical charachters of male and female patients with stage II arterial hypertension (AH) of young and middle age with different gradations of galectin-3 plasma levels according to multiple linear stepwise regression analysis. Materials and methods: 160 patients with AH of different sex (male and female) and age (young (18–44 years), middle (45–60 years)) were examined (clinical, laboratory and instrumental). Multiple linear regression was used to determine the clinical presentation of patients with AH at different levels of the neurohormone (StatSoft's Statistica MultipleRegression v. 10.0 module). which were divided into groups that vi told for the entirely different patient characteristics. multiple linear regression was performed for each indicator separately and the results have been shaped in the form of regression equations. Results. Patients with young and middle-aged AH have been found to be relatively high (RH) levels of galectin-3 associated with: the presence of a complex of metabolic risk factors – obesity and dyslipidemia; in combination with multiple features of structural and functional changes in the cardiovascular system, such as the presence of concentric left ventricular (LV) hypertrophy in combination with myocardial relaxation disorders (Е/e' aver&gt;7.2) and signs of hemodynamic overload of the left atrium (LA) (LA volume index (LAVi)&gt;34 ml/m2); the presence of valve dysfunctions in the form of mitral (1–2 degree) and aortic regurgitation (1 stage); the presence of structural remodeling of the carotid arteries (intima-media thickness (IMT)&gt;0.91 mm). Plasma abdominal obesity was the most informative marker of RH galectin-3 in plasma, IMT&gt;0.91 mm and LAVi&gt;34 ml/m2. Conclusions. The association of plasma galectin-3 levels with various clinical and instrumental indicators indicates a certain effect of the neurohormone on the course of AH in young and middle-aged male and female patients. Of indisputable interest is the determination of the features of the course of AH and the clinical profile of patients at different gradations (relatively low (RL), relatively moderate (RM) and relatively high (RH)) galectin-3 plasma level.

DYNAMICS OF INDICATORS OF ARTERIAL PRESSURE REGULATION AND THEIR DEPENDENCE ON THE LEVELS OF GALECTIN-3 AND ALDOSTERON IN PATIENTS WITH ESSENTIAL HYPERTENSION

This article presents the analysis of the nature of daily blood pressure regulation according to findings of 24-hour monitoring, depending on the levels of two neurohormones, galectin-3 and aldosterone, in the plasma of patients with essential hypertension. Material and methods. According to this goal, the study included 119 (74.4%) patients aged 19-60 years. The diagnosis of essential hypertension was confirmed on the basis of current valid criteria. Each patient underwent a procedure of daily blood pressure monitoring using the apparatus "AVRM-04" Meditech (Hungary). Results and discussion. Aldosterone level was determined by the enzyme-linked immunosorbent assay ELISA using reagents of IBL International GmbH (Canada). The level of galectin-3 in serum was determined by the solid-phase enzyme linked immunosorbent assay using a set of reagents of Human Galectin-3 Platinum ELISA (Bender MedSystems GmbH, Austria). By variation statistics, three plasma levels of galectin-3 were isolated in the main group of patients: the first level was relatively low (&lt;1.1 pg / ml), the second was relatively moderate (from 1.1 to 2, 4 pg / ml) and the third was relatively high level (&gt; 2.4 pg / ml). However, the levels for aldosterone were respectively: the first was relatively low (&lt;206 pg / ml), the second was relatively moderate (from 206 to 325 pg / ml), and the third was relatively high (&gt; 325 pg) / ml). Statistical processing of the findings was processes by additional standard methods from the StatSoft "Statistica" software package V. 12.0. We have found out that in the patients of young and middle age with essential hypertension stage II, the levels of galectin-3 and aldosterone significantly affected the daily regulation of blood pressure. The young and middle-aged patients has relatively high and relatively moderate plasma levels of galectin-3, which can be associated with a significant increase in the heart rate during the day and the heart rate during the night; 24-hour systolic blood pressure (BP), day systolic BP and night systolic BP, 24-hour diastolic BP, day diastolic BP and night diastolic BP, mean PB during the day and mean BP during the night; 24-hour pressure index, pressure index during the day and pressure index during the night; variability of systolic BP during the night, variability of 24-hour diastolic BP, variability of systolic BP during the night; with a decrease in circadian index and 24-hour diastolic BP index; with an increase in the incidence of non-dipper pathological profile registration and a decrease in physiological dipper by changes in both systolic blood pressure and diastolic blood pressure. Conclusion. Aldosterone levels, especially relatively high and relatively moderate, compared to relatively low, are associated with a significant increase in daytime and night time heart rate, 24-hour systolic BP, day and night, 24-hour diastolic BP, and during the night, 24-hour mean BP, as well as during the day and during the night, 24-hour pressure index, as well as pressure index during the day and the night, systolic BP variability at the night, rate of early systolic and diastolic BP rise and decrease in 24-hour systolic and diastolic BP index; with increasing rate of registration of pathological profile “non-dipper” and decrease in “over-dipper” with changes in systolic BP; an increase in the incidence of non-dipper pathological profile registration and a decrease in the normal dipper profile according to diastolic BP. The authors of this study confirm that the research and publication of the results were not associated with any conflicts regarding commercial or financial relations, relations with organizations and/or individuals who may have been related to the study, and interrelations of co-authors of the article.

Association between Galectin-3 levels within central and peripheral venous blood, and adverse left ventricular remodelling after first acute myocardial infarction

Our study investigates association between Galectin-3 levels and adverse left ventricular remodelling (LVR) at six months. Fifty-seven patients following first acute myocardial infarction (AMI) were enrolled in this study and blood samples collected on day 1 from the femoral vein and artery, the right atrium near the coronary sinus and the aortic root, and on day 30, from the cubital vein. Patients with LVESV ≥20% at six months, were included in the LVR group. On day 1, Galectin-3 plasma levels in the femoral vein (10.34 ng/ml ± 3.81 vs 8.22 ng/ml ± 2.34, p = 0.01), and near coronary sinus (10.7 ng/ml ± 3.97 vs 8.41 ng/ml ± 2.56, p = 0.007) were higher in the LVR group. Positive correlations between Galectin-3 levels from aortic root and coronary sinus, aortic root and femoral vein, and coronary sinus and femoral vein, were observed in both groups. On day 30, Galectin-3 concentration in the cubital vein was an independent risk factor of LVR six months post-AMI, demonstrating 1.5-fold increased risk. Day-30 Galectin-3 also showed positive correlations with echocardiography parameters indicative of diastolic and systolic dysfunction. Determining Galectin-3 plasma concentration on day 30 following AMI could have beneficial prognostic value in predicting LVR.

Structural and functional state of left ventricular myocardium in patients with stage II hypertension depending on galectin-3 and aldosterone levels

The analysis of structural and functional state of the left ventricular myocardium was conducted in the article, which concerned the determination of the general morphological and functional echocardiographic parameters of the heart according to the existing recommendations of the American Echocardiographic Society and the European Society of Cardiovascular Imaging; assessment of the relative dimensions/volumes of the LA (left atrium); determination of the structural-geometric remodeling variant of the left ventricular (LV) according to Ganau (1992) also determining the functions of the heart valves in patients with stage II 1-3 degrees hypertension, of different age and gender depending on plasma levels of galectin-3 and aldosterone. Determined the end-systolic (mm) and end-diastolic dimensions of the LV (mm), the thickness of the interventricular septum (mm) and the posterior wall of the LV (mm) in diastole, aortic diameter (AD, mm), size right atrium (RA, mm) and right ventricle (RV, mm), anterior-posterior size of the left atrium (LA, mm) and its index (ILA, mm/m2), LA volume (LPV, ml) and ejection fraction left ventricle (FV globe, %) by the modified Simpson method. LV mass (LVM, g) was estimated by the Penn Convention formula, and LVM index (LVM, g / m2) as the ratio of LVM to body surface area using the Du Bois nomogram (m2). The EchoCG in color Doppler mode measured the early (Ve) and late transmittal (Va) (m\s), their ratio (Ve\Va), the early LF filling time (DT), and the isovolumic LF relaxation time (IVRT) (ms). Statistical processing of the study results was performed using standard methods using the StatSoft Statistica v application package. 12.0 as recommended. In the case of quantitative values, the results were presented as medians and interquartile ranges (25 and 75 percentiles), in the case of relative values, as percentages (%). Comparison of the quantitative values in the groups was performed using the U-Mann-Whitney and Kruskal-Wallis ANOVA test, the relative values by the criterion χ2. A difference of p&lt;0.05 was considered plausible. The obtained data demonstrate that relatively high levels (RH) of both galectin-3 (&gt;2.4 pg/ml) and aldosterone (&gt;325 pg/ml) are identified with significant morphological and functional changes in heart parameters, namely: worse structural-geometric remodeling of LV (increase in cases of concentric hypertrophy (CH) and decrease in cases with normal geometry (NG) of LV). In order to exclude the fact of cross-influence of neurohormones on echocardiographic parameters of the heart, the alignment of the groups in terms of aldosterone and galectin-3 levels was conducted. The analysis turned to be optimal in groups with galectin-3 level of -&gt;2.0 and ≤2.0 pg/ml and aldosterone level of - &gt;290 and ≤290 pg/ml. As a result, it was detected that galectin-3 has a greater pathophysiological effect than aldosterone on such indices as: an increase in aortic diameter; increase in right and left heart chambers dimensions; LVMMI (left ventricular myocardial mass index) value and increase in systolic, diastolic myocardial stress, increase in the number of cases with CH (concentric hypertrophy) and decrease in cases with normal geometry (NG) of LV. Aldosterone level is associated with an increase in dimension/volume indices of LA, calculated per patient’s body area.

Plasma galectin-3 levels do not differ in systemic lupus erythematosus patients.

To investigate the plasma galectin-3 levels in systemic lupus erythematosus (SLE) patients and its relations with clinical and laboratory features. A total of 180 subjects with 90 patients with SLE (8 male, 82 female, mean age 37.86±13.98years) and 90 healthy controls (8 male, 82 female, mean age 36.54±10.89years) were included. Plasma galectin-3 levels were detected by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in age and gender distribution between SLE patients and healthy controls (both P>.05). Plasma galectin-3 level was not significantly different between SLE patients and controls (P=.982) (P>.05). No significant difference was found regarding galectin-3 levels between SLE with nephritis and those without nephritis (P>.05); no significant difference was found between less active SLE and more active SLE (P>.05). Galectin-3 levels were inversely related to immune globulin M (r=-.303, P<.05), while no significant correlation between galectin-3 levels and other quantitative laboratory parameters were observed (all P>.05). In summary, plasma galectin-3 level was not significantly different between SLE patients and controls (P=.982). Further studies are needed to elucidate the role of galectin-3 in SLE.

The relationship between galectin-3 levels and fragmented QRS (fQRS) in patients with heart failure with reduced left ventricular ejection fraction.

Fragmented QRS (fQRS) complex is an electrocardiographic pattern which reflects myocardial scarring. We aimed to investigate the relationship between the presence of fragmented QRS (fQRS) on electrocardiogram (ECG) and plasma galectin-3 levels in patients with heart failure (HF) and severely decreased left ventricular ejection fraction (LVEF≤35%). We prospectively enrolled 125 symptomatic HF patients (NYHA class II-III) with severely reduced LVEF (≤35%). fQRS was identified in ECG. Galectin-3 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured. Patients were divided into two groups based on the presence (n=40) or absence (n=85) of a fQRS on ECG. Majority of patients were male (87.70%), and mean age was 65.1±11.6. Galectin-3 and NT-proBNP levels were found to be significantly higher in the fQRS (+) group compared with the fQRS (-) group (NT-proBNP 5,362±701pg/ml vs. 4,452±698pg/ml; p<0.001, galectin-3 607±89.8pg/ml vs. 509.4±63.5pg/ml; p<0.001). Multivariate analyses revealed galectin-3 and NT-proBNP levels are the presence of fQRS on ECG (p<0.001 and p<0.001, respectively). The area under the curve using the galectin-3 level for fQRS was 0.819. fQRS and serum galectin-3 levels are associated with myocardial fibrosis and are associated with poor prognosis in heart failure. In our study, a positive correlation was found between serum galectin-3 levels and fQRS on ECG.

Galectin-3 plasma levels and its association with the severity of coronary artery disease in chronic stable angina patients.

Galectin-3 plasma levels and its association with the severity of coronary artery disease in chronic stable angina patients.

Sleep apnea and galectin-3: possible sex-specific relationship.

Sleep apnea is associated with increased risk of cardiovascular disease. Elevated plasma galectin-3 levels, a biomarker associated with myocardial fibrosis, are also associated with adverse cardiovascular events, including heart failure. Our objective was to determine the relationship between severity of sleep apnea and plasma levels of galectin-3 and to determine whether this relationship was modified by sex. We performed a cross-sectional study of 471 Mexican Americans from Starr County, TX who underwent an overnight, in-home sleep evaluation, and plasma measurement of galectin-3. Severity of sleep apnea was based on apnea hypopnea index (AHI). Multivariable linear regression modeling was used to determine the association between categories of sleep apnea and galectin-3. We also tested for interactions by sex. The mean age was 53years, and 74% of the cohort was female. The prevalence of moderate to severe sleep apnea (AHI > 15 apnea-hypopnea events per hour) was 36.7%. Moderate to severe sleep apnea was associated with increased levels of galectin-3 in the entire population, but we identified a statistically significant interaction between galectin-3 levels and category of sleep apnea by sex (p for interaction = 0.02). Plasma galectin levels were significantly higher in women with moderate or severe sleep apnea than women with no/mild sleep apnea (multivariable adjusted p < 0.001), but not in men (p = 0.5). Sleep apnea is associated elevated galectin-3 levels in women but not men. Our findings highlight a possible sex-specific relationship between sleep apnea and galectin-3, a biomarker of potential myocardial fibrosis that has been associated with increased cardiovascular risk.

Influence of percutaneous coronary intervention on homocysteine and galection-3 in serum of patients with coronary heart disease and correlation analysis

Objective To discuss the influence of percutaneous coronary intervention(PCI) on the serum concentration of homocysteine(Hcy) and galectin-3 in patients with coronary heart disease(CHD). Methods From September 2016 to October 2017, 70 patients in Ji'nan Central Hospital were selected.According to the results of coronary angiography(CAG), they were divided into observation group with drug-eluted stents(n=47, including 25 cases with type A CHD and 22 cases with type B CHD) and control group without abnormal CAG(n=23). Serial venous blood samples were obtained 1 day before PCI as well as 1 day and 7 days after PCI.Plasma concentrations of Hcy, BNP and galectin-3 were measured and compared.The postoperative patients with PCI were tracked for 1 year to observe the influence of serum Hcy and galectin-3 on the severity of CHD and the quality after PCI. Results The plasma Hcy levels of type A[(16.52±5.41)μmol/L]and type B[(19.32±6.35)μmol/L]after PCI were significantly higher than those of the type A[(11.66±3.25)μmol/L]and the type B[(15.87±5.20)μmol/L]before PCI(t=2.375, P<0.05, t=2.97, P<0.01). Meanwhile, the plasma galectin-3 levels of type A[(0.86±0.11)μg/L] and type B[(1.15±0.48)μg/L]after PCI were also higher than those of the type A[(0.32±0.53)μg/L]and the type B[(0.46±0.19)μg/L]before PCI(t=2.178, P<0.05, t=4.269, P<0.01). Furthermore, levels of the plasma Hcy and galectin-3 were positively associated with the severity of CHD. Conclusion The higher blood levels of serum Hcy, BNP and galectin-3 after PCI indicate that the balloon inflation and implantation of stent can affect the level of plasma Hcy, BNP and galectin-3.Therefore, the levels of serum Hcy and galectin-3 are helpful to diagnose CHD and evaluate the degree of CHD. Key words: Coronary artery disease; Percutaneous coronary intervention; Cysteine; Brain natriuretic peptide; Galectin-3; Coronary angiography; Serum; Degree of the lesion

Combination of Plasma Biomarkers and Clinical Data for the Detection of Myocardial Fibrosis or Aggravation of Heart Failure Symptoms in Heart Failure with Preserved Ejection Fraction Patients.

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms and structural change (including fibrosis). The relationship between novel biomarkers and the above components remains unclear. Methods: Seventy-seven HFpEF patients were recruited. All patients underwent echocardiography with tissue doppler imaging, cardiac magnetic resonance imaging (CMRI), and measurement of plasma inflammatory, remodelling, endothelial function, and heart failure biomarker levels. Myocardial fibrosis was defined by CMRI-extracellular volume. Forward conditional logistic regression was applied to demonstrate the determinants of myocardial fibrosis or heart failure symptoms. Results: The levels of growth differentiation factor, tissue inhibitor of metalloproteinase (TIMP)-1, galectin-3, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were significantly higher in patients with more myocardial fibrosis. Matrix metalloproteinase-2 (MMP-2) and galectin-3 were independent markers of ECV. After adjusting for confounding factors, plasma galectin-3 and MMP-2 levels were correlated with myocardial fibrosis levels (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.02 to 1.09, p = 0.005 and OR: 2.11, 95% CI: 1.35–3.28, respectively), while NT-proBNP level only was associated with heart failure symptoms. We developed a score system consisted of biomarkers and clinical parameters. The area under the curve of the scoring system receiver operating characteristic curve is 0.838 to predict the degree of myocardial diffuse fibrosis. Conclusions: In conclusion, we found that galectin-3 and MMP-2 were significantly associated with global cardiac fibrosis in HFpEF patients. We also combined plasma biomarkers and clinical data to identify HFpEF patients with more severe cardiac fibrosis.

Modified Citrus Pectin Prevents Blood-Brain Barrier Disruption in Mouse Subarachnoid Hemorrhage by Inhibiting Galectin-3.

Background and Purpose- Plasma levels of galectin-3-a matricellular protein-are increased after aneurysmal subarachnoid hemorrhage (SAH), but the functional significance remains undetermined. This study was conducted to evaluate whether modified citrus pectin (MCP; galectin-3 inhibitor) prevents post-SAH early brain injury, focusing on blood-brain barrier disruption. Methods- C57BL/6 male adult mice (n=251) underwent sham or filament perforation SAH modeling, followed by a random intracerebroventricular injection of vehicle or drug at 30 minutes post-modeling. First, vehicle-treated and 0.8, 4, 16, or 32 µg MCP-treated mice were assessed by neuroscore and brain water content at 24 and 48 hours post-modeling. Second, Evans blue extravasation, Western blotting, coimmunoprecipitation and immunostaining were performed in vehicle-treated or 4 µg MCP-treated mice at 24 hours post-modeling. Third, vehicle or R-galectin-3 (recombinant galectin-3) was administered to SAH mice simultaneously with vehicle or MCP, and neuroscore and Evans blue extravasation were evaluated at 24 hours post-modeling. Fourth, vehicle or R-galectin-3 was administered to MCP-treated SAH mice at 24 hours, and neuroscore and IgG immunostaining were evaluated at 48 hours post-SAH. Results- Among tested dosages, 4 µg MCP showed the best neuroprotective effects as to preventing neurological impairments and brain edema at 24 to 48 hours post-SAH. Four micrograms MCP attenuated post-SAH blood-brain barrier disruption and galectin-3 upregulation in brain capillary endothelial cells, associated with inactivation of ERK (extracellular signal-related kinase) 1/2, STAT (signal transducer and activator of transcription)-3, and MMP (matrix metalloproteinase)-9, and the consequent preservation of a tight junction protein ZO-1 (zonula occludens-1). Coimmunoprecipitation assay demonstrated physical interactions between galectin-3 and TLR (Toll-like receptor) 4. R-galectin-3 blocked the neuroprotective effects of MCP. Conclusions- MCP prevents post-SAH blood-brain barrier disruption possibly by inhibiting galectin-3, of which the mechanisms may include binding to TLR4 and activating ERK1/2, STAT-3, and MMP-9. This study suggests galectin-3 to be a novel therapeutic target against post-SAH early brain injury.

Soluble CD163 was linked to galectin-3, diabetic retinopathy and antidepressants in type 1 diabetes

ObjectiveDepression has been associated with diabetic retinopathy and increased plasma levels of galectin-3, a lectin expressed in activated macrophages. Increased levels of sCD163, the soluble form of a macrophage expressed scavenger receptor involved in several inflammatory processes, have been demonstrated in the vitreous of the eye in type 1 diabetes (T1D) patients with severe diabetic retinopathy. The aim was to explore whether circulating sCD163 was associated with diabetic retinopathy, depression and/or galectin-3 in T1D patients, controlling for gender, metabolic factors, other diabetes complications, life style and medication.DesignCross sectional.MethodsTwo hundred eighty-seven T1D patients, men 56%, age 18–59 years, diabetes duration ≥1 year, were consecutively recruited from one specialist diabetes clinic. Depression was assessed by Hospital Anxiety and Depression Scale-Depression subscale. Blood samples, anthropometrics and blood pressure values were collected, supplemented with data from electronic medical records and the Swedish National Diabetes Registry. High plasma sCD163 was defined as ≥0.575 mg/L (corresponding to the 80th percentile) and high plasma galectin-3 as ≥4.659 µg/L (corresponding to the 95th percentile).ResultsThe prevalence of depression was 10%, antidepressant medication 8%, diabetic retinopathy 72%, high sCD163 20% and high galectin 3 5%. High galectin-3 (AOR 9.7), antidepressants (AOR 3.8), diabetic retinopathy (AOR 2.4) and systolic blood pressure (per mmHg) (AOR 1.03) were associated with high sCD163.ConclusionsThis is the first study to show that circulating sCD163 was independently associated with galectin-3, the use of antidepressants and diabetic retinopathy, in patients with T1D. Depression was not associated with sCD163.

Galectin-3 as a potential marker of myocardial hypertrophy in essential hypertension in individuals with polymorphic AT1R genotypes

Background: The potential use of plasma galectin-3 level as a of myocardial changes in the development of hypertrophy in males with essential hypertension (EH), carriers of polymorphic variants of II type 1 receptor gene, was studied. The level of brain peptide (BNP), as well as the parameters of central and systemic, and structural and functional parameters of the heart in carriers of polymorphic variants of II type 1 receptor gene, were studied as reference.&#x0D; Methods: The study included 79 individuals with no signs of cardiovascular disease, and 62 males with stage II EH, aged 40-60, who were residents of Ukraine. All patients were treated at the Military Medical Clinical Center of Central Region of Air Forces of Ukraine and Vinnytsia Regional Specialized Clinical Hospital of Radiation Protection of the Ministry of Health of Ukraine, from December 2013 to June 2015. The patients were studied during their treatment at the in-patient department. Anesthetic, clinical and laboratory findings, and measures were entered into a special chart. Biochemical analyses were done upon admission of the patients to the hospital. Immunologic, and instrumental methods of examination were used as well. Statistical analyses of the results obtained were done on a personal computer using standard statistical package STATISTICA 10. Microsoft Excel was used for primary preparations of tables and intermediate calculations.&#x0D; Results: In patients with EH and myocardial hypertrophy, the C allele of angiotensin II type 1 receptor gene was found to be dominating. They had higher levels of both galectin-3 and BNP. The threshold levels of galectin-3 and BNP for screening diagnosis of EH with myocardial hypertrophy in males (who were residents of the Podillya region of Ukraine) were evaluated.