Galectin-3 Concentrations Research Articles

Heart failure patients with implantable cardioverter-defibrillator: molecular predictors for risk assessment of adverse events

Abstract Funding Acknowledgements Type of funding sources: None. Objective. The objectives of the study were to evaluate a multimarker strategy including galectin-3, soluble ST2 (sST2) and NT-proBNP for risk stratification of adverse cardiovascular events (ACE) and death in heart failure (HF) patients with implantable cardioverter-defibrillator (ICD) during the 12-month follow-up period. Methods. A total of 57 patients (41 men, median age of 65 [59; 68] years) of New York Heart Association (NYHA) class II-IV and baseline LVEF of 34% [26; 44]% were enrolled in the study. 71% of patients had prior myocardial infarction and 86% received prior myocardial revascularization (coronary artery bypass graft/stent). Serum levels of sST2, NT-proBNP and galectin-3 were measured using an enzyme immunoassay at baseline. All patients received implantation of cardioverter-defibrillator. Results. After the 12-month follow-up period, all patients were divided into 2 groups: group A (n = 17) comprised patients with ASE, group B (n = 40) comprised those without it. During 12-month follow-up period 15.8% of patients (n = 9) died. The median values of sST2 in group A were higher (p = 0.001) by 51% than in group B (24.42 [22.46; 31.4] and 49.94 [37.4; 58.54] ng/mL, respectively). The median values of galectin-3 in group A (p = 0.002) were 14.7 [9.95; 24.3] ng/L and 9.2 [7.2; 14.7] ng/L in group B. The median values of NT-proBNP were also higher (p = 0.021) by 22% in patients with ASE. Odds ratio for hyperexpression of sST2 was 3.06 (95% CI 2.89-3.17; p <0.0001), 3.79 for galectin-3 (95% CI 2.67-4.11; p < 0.001), and 1.27 for NT-proBNP (95% CI 0.89-2.21; p = 0.036). Reclassification did not significantly benefit after NT-proBNP addition into the full model; some indices even worsened with all 3 biomarkers. Based on ROC-analysis, baseline sST2 concentration of 34.43 ng/mL (sensitivity of 86.7%, specificity of 71.9%, and AUC of 0.78; p < 0.0001) and baseline galectin-3 concentration of 11.6 ng/L (sensitivity of 67.5%, specificity of 70.6%, and AUC of 0.72; p = 0.0014) were identified as a cut-off values predicting adverse cardiac events. The combined evaluation of both biomarkers increased the predictive value of the analysis (sensitivity of 90.1%, specificity of 79.1%, and AUС of 0.84; p < 0.0001). Conclusion. Our data suggest that ST2 and galectin-3 may be used as diagnostic biomarkers in HF patients with ICD. The combined use of sST2 and galectin-3 demonstrated higher diagnostic sensitivity and specificity for prediction of adverse outcomes. However, NT-proBNP in addition to ST2 and galectin-3 biomarkers had a limited effect on risk stratification.

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

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

Evaluation of galectin-3, peptidylarginine deiminase-4, and tumor necrosis factor-α levels in gingival crevicular fluid for periodontal health, gingivitis, and Stage III Grade C periodontitis: A pilot study.

Comparing the gingival crevicular fluid (GCF) levels of galectin-3, peptidylarginine deiminase 4 (PAD4) and tumor necrosis factor-alpha (TNF-α) in individuals with stage III grade C periodontitis and gingivitis and with healthy periodontium was the purpose of this clinical research. Sixty systemically healthy and non-smoker individuals consisting of stage III grade C periodontitis (group S3P/n=20), gingivitis (group G/n=20), and periodontally healthy (group HP/n=20) were recruited for this research. Clinical parameters such as probing depth, clinical attachment level, gingival index, plaque index, and bleeding on probing were recorded in periodontal charts. Enzyme-linked immunosorbent assay method was used in evaluating the GCF levels of galectin-3, PAD4, and TNF-α for study groups. The GCF galectin-3 total amount was highest in group S3P compared with group G and group HP (P<0.05). Its total amount was also higher in group G compared with group HP (P<0.05). The GCF PAD4 total amount was higher in group S3P compared with group HP (P<0.05) but was similar with group G (P >0.05). Its total amounts were also similar in group G and group HP (P >0.05). The GCF TNF-α total amounts were similar in group S3P and group G (P >0.05) but significantly greater than the group HP (P ˂0.05). The GCF galectin-3, PAD4, and TNF-α concentrations were lower in the group S3P and group G compared with the group HP (P<0.05). There were significant positive correlations between GCF galectin-3 total amount and all clinical parameters (P ˂0.01) and also between GCF galectin-3 and TNF-α total amounts (P ˂0.01). There was no correlation between PAD4 and clinical parameters, or between PAD4 and TNF-α (P >0.05). Galectin-3 and PAD4 may be involved in the periodontal disease pathogenesis considering the elevated levels of these molecules in periodontal disease. These biomarkers may be used in the diagnosis of periodontal diseases.

The Expression and Function of Metastases Associated Lung Adenocarcinoma Transcript-1 Long Non-Coding RNA in Subchondral Bone and Osteoblasts from Patients with Osteoarthritis.

Metastasis Associated Lung Adenocarcinoma Transcript-1 (MALAT1) is implicated in regulating the inflammatory response and in the pathology of several chronic inflammatory diseases, including osteoarthritis (OA). The purpose of this study was to examine the relationship between OA subchondral bone expression of MALAT1 with parameters of joint health and biomarkers of joint inflammation, and to determine its functional role in human OA osteoblasts. Subchondral bone and blood were collected from hip and knee OA patients (n = 17) and bone only from neck of femur fracture patients (n = 6) undergoing joint replacement surgery. Cytokines were determined by multiplex assays and ELISA, and gene expression by qPCR. MALAT1 loss of function was performed in OA patient osteoblasts using locked nucleic acids. The osteoblast transcriptome was analysed by RNASeq and pathway analysis. Bone expression of MALAT1 positively correlated to serum DKK1 and galectin-1 concentrations, and in OA patient osteoblasts was induced in response to IL-1β stimulation. Osteoblasts depleted of MALAT1 exhibited differential expression (>1.5 fold change) of 155 genes, including PTGS2. Both basal and IL-1β-mediated PGE2 secretion was greater in MALAT1 depleted osteoblasts. The induction of MALAT1 in human OA osteoblasts upon inflammatory challenge and its modulation of PGE2 production suggests that MALAT1 may play a role in regulating inflammation in OA subchondral bone.

Analysis of galectin-3 levels as a source of coronary heart disease risk during periodontitis.

Different evidence has shown that Galectins have a key role as modulators of cell surface functions and signaling in a wide range of inflammatory diseases during their preclinical stages. The aim of this study was to analyze the association and impact of periodontitis and coronary heart disease (CHD) on salivary and serum Galectin-3 in patients with periodontitis and CHD. For the present study, healthy controls (n=38), periodontitis (n=40), CHD (n=39), and a combination of periodontitis +CHD (n=38) patients were enrolled and analyzed. In each patient, demographic characteristics and a full-mouth clinical periodontal examination were achieved. Moreover, serum and salivary samples were collected to assess Galectin-3 and Endothelin-1 (ET-1) levels. The Jonckheere-Terpstra p-trend and Spearman's correlation tests as well as uni- and linear regression analyses were used to analyze the study data. Patients with periodontitis (serum, p=.003; saliva, p<.001) and periodontitis + CHD groups (serum p=.004; saliva, p<.001) had higher median serum and salivary concentrations of Galectin-3 in comparison with CHD and healthy controls. Serum (p=.006) and salivary (p=.009) Galectin-3 levels were significantly correlated with serum ET-1. The multivariate regression analysis highlighted that periodontitis (p=.047) was the significant predictor of serum Galectin-3 levels while ET-1 (p=.028) was the significant predictor of salivary Galectin-3 levels. The results showed that patients with periodontitis and periodontitis + CHD presented significant higher serum and salivary Galectin-3 levels in comparison with CHD patients and healthy subjects. Periodontitis and ET-1 were the significant predictors of serum and salivary Galectin-3 levels, respectively.

Metabolic mediators determine the association of antinuclear antibody subtypes with specific clinical symptoms in systemic sclerosis

PurposeThe aim of this study was to investigate the possible link between different types of systemic sclerosis-specific antinuclear antibodies, adipokines and endothelial molecules which were recently found to have a pathogenic significance in systemic sclerosis. Materials/methodsSerum concentration of adiponectin, resistin, leptin, endothelin-1, fractalkine and galectin-3 were determined in the sera of patients with systemic sclerosis (n ​= ​100) and healthy controls (n ​= ​20) using ELISA. ResultsThe following associations between antinuclear antibodies and increased serum concentrations were identified: anticentromere antibodies with endothelin-1 (p ​< ​0.0001; mean level in patients 2.21 vs control group 1.31 ​pg/ml), anti-topoisomerase I antibodies with fractalkine (p ​< ​0.0001; 3.68 vs 1.68 ​ng/ml) and galectin-3 (p ​= ​0.0010, 6.39 vs 3.26 ​ng/ml). Anti-RNA polymerase III antibodies were associated with increased resistin (p ​< ​0.0001; 15.13 vs 8.54 ​ng/ml) and decreased adiponectin (p ​< ​0.0001; 2894 vs 8847 ​ng/ml). ConclusionIn systemic sclerosis metabolic and vascular factors may serve as mediators between immunological abnormalities and non-immune driven clinical symptoms.

The expression of Galectin-3 in breast cancer and its association with metastatic disease: a systematic review of the literature.

Breast cancer is the most common form of cancer and the second highest cause of cancer mortality in female patients. The significance of the expression of Galectin-3 has been correlated with various malignancy types and in data from several research papers, the expression of Galectin-3 has been associated with the progression and metastasis of breast cancer. In the present study, the authors' goal is to identify whether the expression of Galectin-3 in breast cancer can be associated with the presence and/or recurrence of a metastatic disease. Both Scopus and PubMed databases were utilized, by inputting the following combination of keywords: (((Breast) AND Metastasis)) AND ((Galectin 3) OR Galectin-3). The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. We included one case-control study, three retrospective case studies and one retrospective cohort study. In two of the included studies, the levels in concentration of Galectin-3 were not correlated with a significant difference in prognosis. In two studies, the lacking in expression of Galectin-3 was associated with a worse prognosis and in one of the studies selected, the elevated levels of Galectin-3 were correlated with recurrence of disease in triple negative breast cancer cases. For most of the studies selected for this review, the results were contradictory in regard to the role of Galectin-3 for prognosis and metastatic potential in female breast cancer patients. It is still unclear, whether Galectin-3 can be used as a prognostic marker for advanced breast cancer disease.

Increased Severity of Ulcerative Colitis in the Terminal Phase of the Metabolic Syndrome.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

Регрессионный анализ взаимосвязи галектина-3 с факторами, ухудшающими течение хронической сердечной недостаточности у пациентов с ревматоидным артритом

Aim of study. To reveal the most significant risk factors of chronic heart failure (CHF) decompensation against the background of rheumatoid arthritis (RA) and to carry out a regression analysis of galectin-3 level. Material and methods. Study group: 134 CHF RA patients; comparison group: 122 CHF patients without RA. The functional CHF class of the study participants was I-II according to the NYHA. The RA diagnosis was established based on X-ray examination and serological testing including determination of the rheumatoid factor, antibodies to the cyclic citrullinated peptide and C-reactive protein. The activity of the inflammatory process was evaluated using the DAS28 index and the visual analogue scale for pain. The X-ray stage of RA was I-III according to Steinbrocker classification in all patients enrolled. The medicines for CHF treatment were comparable in the groups. The disease-modifying anti-rheumatic drug was methotrexate. Patients who did not receive methotrexate due to development of adverse effect and/or individual intolerance were administered 20mg leflunomide per day. Additionally, NSAIDS were used (enteral, parenteral, local application). Haematological, biochemical and instrumental tests were used. The data processing was performed via the STATISTICA 10.0 software; the paper presents statistically reliable results. The significance level was set at p&lt;0.05. Results. As a result, logistic regression analysis revealed statistically significant associations between galectin-3 and the level of atrial natriuretic peptide (r=0.3; beta=0.36; p=0.02), triglycerides (r=0.3; beta=0.6; p=0.04), low-density lipoproteins (r=0.3; beta=0.2; p=0.001) and the glomerular filtration rate (r=0.5; beta=0.3; p=0.01). Conclusion. The analysis has revealed data pointing to the possibility of heart failure compensation against the background of RA at the level of galectin-3 concentration of 17.6ng/ml or higher. The regression model attests to the association between the cytokine levels observed and the possible destabilisation of dyslipidaemia progression, kidney function and water-salt metabolism.

Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure.

Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. ACTRN12610000374066.

Evaluation of galectins 1 and 3 expression in canine melanoma

ABSTRACT: Canine melanoma is a frequently-occuring neoplasm in dogs and presents as malignant and highly metastatic in this context, studies that contribute to the understanding of the tumor microenvironment in melanoma include the role of galectins. Galectins are proteins of the family of animal lectins that display carbohydrate recognition domains. Galectin-1 and galectin-3 are associated with neoplastic transformation, neoplastic cell survival, angiogenesis, immune system evasion, and metastasis. The goal of this study was to establish a correlation between expression patterns of galectin-1 and galectin-3 and the different degrees of aggressiveness of canine melanoma, as well as to determine serum concentration of galectin-3 in dogs with melanoma. Galectin-1 and galectin-3 expression was analyzed by immunohistochemistry in 30 canine melanomas, six melanocytomas and nine metastatic lymph nodes from patients whose primary tumors were also processed and analyzed. Serum samples from 30 dogs were collected and galectin-3 concentration was determined by ELISA and compared to the samples of 10 healthy dogs. Canine melanoma samples expressed galectin-1 in the cytoplasm and presented a variable pattern of galectin-3 staining depending on melanoma aggressiveness. We observed a decrease in the percentage of cells with cytoplasmic galectin-3 immunolabeling simultaneous to the increased nuclear staining intensity, while there was also a decrease in the percent frequency of nuclear galectin-3 immunolabeled cells according to progression of melanoma, comparing the least to the most aggressive cases. Dogs with melanoma had increased serum levels of galectin-3 when compared to healthy animals, suggesting its potential biomarker of patients with melanoma.

Multiple biomarkers measurement to estimate the duration of atrial fibrillation.

An accurate estimation of the duration of atrial fibrillation is critical for its safe management. Recent studies suggested that copeptin, carbohydrate antigen-125, galectin-3 and growth differentiation factor-15 are increased in atrial fibrillation. We examined the ability of these markers to identify patients presenting with atrial fibrillation of ≤48 versus >48 h duration. Retrospective analysis of a prospective study that included patients with atrial fibrillation of known duration. A total of 98 patients were analysed, 47 with atrial fibrillation ≤48 h and 51 with >48 h. In patients presenting with atrial fibrillation of ≤48 versus >48 h duration, the mean carbohydrate antigen-125 concentration was 16.9 ± 12.5 versus 30.9 ± 36.3 U/mL (P = 0.01), and growth differentiation factor-15 concentration was 1320 ± 889 versus 2608 ±2163 pg/mL (P < 0.001). Copeptin concentration was not independently associated with atrial fibrillation duration. The galectin-3 concentration did not differ between groups. Area under the ROC curve to identify patients with atrial fibrillation ≤48 h was 0.869 for carbohydrate antigen-125, 0.853 for growth differentiation factor-15. The plasma concentrations of carbohydrate antigen-125, growth differentiation factor-15 and copeptin, but not galectin-3, are higher in patients presenting with atrial fibrillation of >48 h duration than in those with atrial fibrillation ≤48 h. The ability to discriminate recent atrial fibrillation offered by carbohydrate antigen-125 and growth differentiation factor-15 seems high.

Galectin-1 is associated with the severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography

Galectin-1, a β-galactoside-binding lectin mediating inflammation and neovascularization, is reported to attenuate ventricular remodeling after myocardial infarction. But its role in stable coronary artery disease (CAD) has not been fully elucidated. This study aimed to identify the relationship between the circulating galectin-1 level and the severity of CAD in patients with suspected CAD. Pre-procedure galectin-1 and high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in 834 subjects who underwent scheduled coronary angiography. Subjects were grouped into tertiles of the galectin-1 levels. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019 or the occurrence of major adverse cardiovascular events (MACE). Patients with higher galectin-1 concentrations were older; had greater prevalence of hypertension, diabetes, chronic kidney disease, and heart failure; and were more likely to present with higher hs-CRP levels and SYNTAX scores. During the follow-up period of 1.3 ± 1.1 years, patients in the highest tertile of galectin-1 were associated with a greater risk of MACE after adjustment for age, sex, comorbidities, co-medications, serum levels of hemoglobin, creatinine, hs-CRP, ejection fraction, SYNTAX scores, and revascularization modalities (adjusted hazard ratio 10.95, 95% confidence interval 2.29–52.47, p = 0.003). Galectin-1 showed better discriminatory performance than hs-CRP, and non-inferior performance to SYNTAX scores, in predicting the incidence of MACE.

Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes

Aim. To study molecular biomarkers in patients with type 2 diabetes (T2D) in combination with heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) and compare the data obtained with clinical characteristics of myocardial remodeling.Material and methods. The study included 42 patients with T2D (men — 53%, mean age — 60 years) with clinical manifestations of class II HF: 29 patients with HFpEF (group 1) and 13 patients with HFmrEF (group 2). The control group consisted of 13 healthy people, which were comparable in sex and age and had a normal body mass index (BMI). Patients received stable glucose-lowering and optimal drug therapy for HF for 3 months prior to enrollment in the study. Patients with HFpEF and HFmrEF were comparable in clinical and demographic parameters, had glycated hemoglobin (HbA ) of 8,5% and 8,8%, respectively (p&gt;0,05), increased BMI or grade I-II obesity.We studied following biomarkers: NT-proBNP, highly sensitive C-reactive protein (hsCRP), sST2, galectin-3, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1).Results. Volumetric parameters of the left ventricle (LV),LV mass indexed to growth and NT-proBNP were higher in the group of HFpEF patients (p&lt;0,05 for all). The concentrations of galectin-3, PICP were higher, and the MMP-9/TIMP-1 ratio decreased in patients with T2D compared with the control group (p&lt;0,05 for all). PICP values were higher in patients with HFmrEF compared with patients with HFpEF (106,4 (85,4; 140,4) ng/ml vs 46,8 (12,6; 98,6 ng/ml), respectively, p=0,043). In patients with T2D and HF, a relationship was found between TIMP-1 andLV end-diastolic volume (r=-0,68; p=0,042).Conclusion. Patients with HFmrEF and T2D have higherLV volume and mass, higher concentrations of NT-proBNP and PICP in comparison with patients with HFpEF. The direction of MMP-9/TIMP-1 changes may reflect a decrease in antifibrotic processes. Further prospective studies on large samples using a multiple biomarker model are required in T2D and various HF phenotypes.

Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis.

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF (p = 0.01 and p = 0.03, respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF (p = 0.043 and p = 0.033, respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area (r = −0.58, p = 0.001), PIIINP, TIMP-1, and LV end-diastolic volume (r = −0.68 and p = 0.042 and r = 0.38 and p = 0.02, respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.

Diagnostic Power of Galectin-3 in Rheumatic Diseases.

Background: The purpose of our study was to assess the diagnostic power of galectin-3 and compare its between rheumatic diseases and with routinely used tests such as CRP and ESR. Methods: Eighty-two patients with rheumatoid arthritis (RA), 49 patients with systemic sclerosis (SSc), and 18 patients with systemic lupus erythematosus (SLE) were enrolled in this study. The control group comprised 30 healthy controls. Serum galectin-3 concentration was measured using immunochemical method. Results: The galectin-3 concentration were significantly elevated in the RA, SSc, and SLE in comparison to the controls (p = 0.000, p = 0.000, p < 0.001; respectively). However, there were no significant differences in the serum galectin-3 levels between rheumatic diseases (H = 0.395, p = 0.821). In RA and SSc patients, galectin-3 positively correlated with erythrocyte sedimentation rate (R = 0.332, p = 0.004; R = 0.384, p = 0.009; respectively). ROC analysis revealed that galectin-3 had an excellent diagnostic power in RA (AUC = 0.911) and SSc (AUC = 0.903) and very good for SLE (AUC = 0.859). Conclusion: We concluded that diagnostic power of serum galectin-3 is as great as CRP and ESR in rheumatic diseases and it can be a very good laboratory marker in RA and SSc patients and a useful tool in the diagnosis of SLE.

Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity

Galectin-3 is a biomarker of fibrosis, inflammation and oxidative stress, and its role in heart remodelling and exercise intolerance has not been conclusively proven in heart failure (HF) patients with reduced ejection fraction (rEF). We prospectively assessed 67 consecutive patients with symptomatic HF and left ventricular (LV) EF ≤ 35% during optimal medical therapy, with a mean serum galectin-3 concentration of 15.3 ± 6.4 and a median of 13.5 ng/mL. The group with galectin-3 concentrations greater than or equal to the median had significantly worse right ventricular (RV) systolic function parameters (s′, TAPSE), higher pulmonary artery systolic pressure, more advanced tricuspid regurgitation and lower RV-to-pulmonary circulation coupling index, while no significant differences were found in LV parameters. Moreover, this group achieved significantly lower parameters in cardiopulmonary exercise testing. Significant negative correlations were found between galectin-3 concentration and RV parameters and exercise capacity parameters and have persisted after adjustment for glomerular filtration rate, but not all of them have persisted after adjustment for NT-proBNP. Multivariate regression analysis revealed that TAPSE (β coefficient: − 0.605; p < 0.001) and heart rate at peak exercise (β coefficient: − 0.98; p = 0.009) were independently related to galectin-3 concentration. Elevated galectin-3 concentration in patients with HFrEF might indicate concomitant RV dysfunction and exercise intolerance.

The role of galectin-1 and galectin-3 in the mechanisms of T-cell immune response dysregulation in colon cancer

The aim of the study was to characterize the features of the subpopulation composition and cytokine-secretory activity of T lymphocytes (Th1, Th17 and Treg) in relation to the concentration of galectin-1 and galectin-3 in the blood of patients with colon cancer. Materials and methods. A total of 26 patients diagnosed with colon cancer were examined. The study material included whole peripheral blood, blood plasma, and supernatants of suspension cultures of mononuclear leukocytes. Lymphocytes isolated from blood were typed by flow cytometry using monoclonal antibodies. The content of galectin-1 and galectin-3 (in blood plasma) and IFNγ, IL-17A, and TGFβ (in supernatants of mononuclear leukocyte culture in vitro ) were determined by enzyme-linked immunosorbent assay. The results obtained were analyzed by statistical methods. Results. In patients with colon cancer, a significant increase in the concentration of galectin-1 and galectin-3 in the blood plasma was found, which was associated with a decrease in the content of CD4+T-bet+ Th1 lymphocytes, CD4+RORC2+ Th17 lymphocytes in the blood and in vitro hyposecretion of IL-17. At the same time, positive correlations were revealed between the concentration of galectin-1 and galectin-3, the content of CD4+FoxP3+ Treg cells in the blood, and the secretion of TGFβ by mononuclear leukocytes in vitro . Conclusion. In colon cancer, increased levels of galectin-1 and galectin-3 in the blood are associated with quantitative deficiency and inhibited secretory activity of effector T lymphocytes and activation of the immunosuppressive functions of regulatory T cells. These results suggest a negative role of galectin 1 and galectin 3 in the mechanisms of regulation of the T cell immune response in colon cancer.

Correlation between microRNA expression levels and plasma concentrations of biomarkers of post-transplant complications in heart transplant recipients

Objective: to analyze the correlation between the expression levels of microRNA-101, microRNA-142, microRNA-27, microRNA-339, and microRNA-424 and the plasma concentrations of biomarkers that are potentially significant for the diagnosis of post-transplant complications in heart recipients. Materials and methods. The study enrolled 72 heart recipients, among whom were 56 men (77.8%). The average age of recipients was 48.6 ± 10.9 (16 to 70) years. There were 38 patients with severe chronic heart failure, among whom were 29 men (76.3%). Patients’ mean age was 48.8 ± 9.9 (26 to 70) years. The control group consisted of 12 healthy individuals who did not differ significantly by sex and age. microRNA expression levels in blood plasma were measured via quantitative polymerase chain reaction. Plasma concentrations of VEGF-A, PLGF, MCP-1, and sCD40L were determined using a multiplex method. ST2 and Galectin-3 concentrations were measured via enzyme-linked immunosorbent assay. Results. Patients with end-stage chronic heart failure were found to have significantly higher expression levels of microRNA-27, microRNA-339 and microRNA-424 in blood plasma compared with the healthy individuals. In potential heart recipients, the expression le vels of microRNA-339 and microRNA-424 correlated with serum galectin-3 concentrations, microRNA-101 expression levels correlated with PLGF-1 concentrations, while microRNA-27 expression levels correlated with plasma MCP-1 concentrations. In the early post-transplant period, the expression levels of microRNA-101, microRNA-339, and microRNA-424 in heart recipients were significantly lower than in patients with severe chronic heart failure. In the early post-transplant period (one year or more after transplantation), microRNA-101 and microRNA-27 expression levels were significantly higher than in heart recipients. A year or more after transplantation, the following correlations were found in heart recipients: microRNA-142 expression level correlated with serum levels of galectin-3 (p = 0.05), microRNA-27 and microRNA-424 expression levels correlated with ST2 concentrations (p = 0.02), microRNA-27 expression level correlated with PLGF-1 concentrations (p = 0.02), while microRNA-101 expression level correlated with serum levels of PAPP-A (p = 0.05). Conclusion. In heart recipients, the expression levels of microRNA-142, microRNA-27, microRNA-424, and microRNA-101 correlate with the concentration levels of biomarkers of fibrosis (Galectin-3), rejection (ST2), neoangiogenesis (PLGF), and tissue destruction (PAPP-A). A comprehensive analysis of pre- and post-translational markers may open up new perspectives in diagnosis, assessment of the risks of post-transplant complications, and in understanding the processes leading to their development.

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.