Galectin-3 Concentrations Research Articles

Waterpipe smoke inhalation induces lung injury and aortic endothelial dysfunction in mice.

Waterpipe tobacco smoking (WPS) inhalation has been shown to trigger endothelial dysfunction and atherosclerosis. However, the mechanisms underlying these effects are still unknown. Here, we assessed the impact and underlying mechanism of WPS exposure for one month on endothelial dysfunction using aortic tissue of mice. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Inhalation of WPS induced an increase in the number of macrophages and neutrophils and the concentrations of protein, tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1beta, and glutathione in bronchoalveolar lavage fluid. Moreover, the concentrations of proinflammatory cytokines (TNF alpha, IL-6 and IL-1beta), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and P-selectin) and markers of oxidative stress (lipid peroxidation, glutathione, superoxide dismutase and nitric oxide) in aortic homogenates of mice exposed to WPS were significantly augmented compared with air exposed mice. Likewise, the concentration of galectin-3 was significantly increased in the aortic homogenates of mice exposed to WPS compared with control group. WPS inhalation induced vascular DNA damage assessed by comet assay and apoptosis characterized by a significant increase in cleaved caspase-3. While the aortic expression of phosphorylated nuclear factor kappaB (NF-kappaB) was significantly increased following WPS inhalation, the concentration of sirtuin 1 (SIRT1) was significantly decreased in WPS group compared with air-exposed group. In conclusion, our study provided evidence that WPS inhalation triggers lung injury and endothelial inflammation, oxidative stress and apoptosis which were associated with nuclear factor-kappaB activation and SIRT1 down-regulation.

Long-Term Changes in the Biomarkers of Left Atrial Fibrosis after Pulmonary Vein Isolation for Paroxysmal and Persistent Atrial Fibrillation.

Atrial fibrillation (AF) is accompanied by inflammation and fibrosis to variable extent. The biomarkers of fibrosis were measured in patients with different forms of AF and cardiac status. Herein, we assessed the associations of the baseline concentrations of different biomarkers with the long-term success of pulmonary vein isolation (PVI) in patients with a structurally normal heart. Furthermore, we compared biomarker levels before and 3 years after ablation to gain further insights into the AF mechanism. Patients, undergoing PVI for paroxysmal/persistent AF were enrolled prospectively. Blood samples were obtained 24 hours before and 3 years after ablation. Serum cancer antigen 125 (CA-125), plasma Caspase-3, Galectin-3 and Cathepsin L concentrations were measured. Follow-up visits every 6 months included 12-lead electrocardiogram, 24-hour Holter, trans-telephonic monitoring as well as transthoracic echocardiography after ablation. Biomarker levels, left ventricular ejection fraction and left atrial (LA) diameters at baseline and at the 3-year follow-up were compared in patients with versus without AF recurrence. A total of 63 patients were enrolled (23 women; age 61.4 ( 8.8) years). The acute isolation of all pulmonary veins was achieved in all patients. During a mean follow-up of 36.3 6.3 months, AF recurrence was demonstrated in 26 (41.3%) patients. No significant differences were demonstrated in the levels of CA-125, Galectin-3, Caspase-3 and Cathepsin L pre- and post-ablation in patients with versus without AF recurrence. A significant decrease was detected in the concentrations of Caspase-3, Galectin-3 and Cathepsin L during follow-up with no difference in patients with versus without AF recurrence. A positive correlation was found between Caspase-3 levels and LA diameters in the AF recurrence group both before (r = 0.477; p = 0.018) and after the procedure (r = 0.533; p = 0.019). Our results demonstrated that the levels of CA-125, Caspase-3, Cathepsin L and Galectin-3 are not associated with AF recurrence after PVI in patients with a structurally normal heart and mainly paroxysmal AF. Except for CA-125, all the other biomarkers demonstrated a significant decrease during a 3-year follow-up post-ablation. Furthermore, Caspase-3 levels demonstrated a positive correlation with LA dimensions in patients with AF recurrence.

Galectin-9 influences the Tim-3 molecule expression in natural killer different subpopulations

Galectin-9 is a b-galactoside binding lectin with expressed immunoregulatory activity. During pregnancy galectin-9 is produced by trophoblast cells and regulates the function of natural killer (NK) cells at the maternal-fetal interface via binding to Tim-3 (T-cell Ig and mucin domain-containing protein 3) molecules. Natural killer (NK) lymphocytes belong to the innate lymphoid cells, which have a cytotoxic effect on target cells and are capable of producing a large number of regulatory factors (cytokines, chemokines). Decidual NK have a tolerant phenotype and play a leading role in the regulation of invasive trophoblast growth and provide peripheral immune tolerance in the area of uteroplacental contact. Peripheral NK cells express Tim-3 molecules. Galectin-9 concentration is increased in peripheral blood during physiologic pregnancy. At pregnancy phenotype and functions of peripheral NK cells are changed to maintain the maternal–fetal immune tolerance. Peripheral NK cells migrate to the maternal-fetal interface and are transformed into a decidual NK-like phenotype cells. Galectin-9 concentration is decreased in women with a complicated pregnancy and miscarriage. However the galectin-9 effects on different NK cell subpopulations of peripheral blood are not investigated. Therefore, we studied the galectin-9 influence on phenotype transformation and Tim-3 expression of NK cells isolated from peripheral blood of healthy non-pregnant fertile women. CD56+NK cells were obtained by immunomagnetic separation and cultivated in vitro during 72 hours with cytokines (IL-2 and IL-15). Galectin-9 (5 ng/mL) and anti-Tim-3 (10 mg) antibodies were added to the NK cultures. Galectin-9 concentration is corresponded to its level during first trimester of physiologic pregnancy. The number of regulatory NK (CD16-CD56bright), cytotoxic NK (CD16+CD56dim/-) cells and Tim-3 expression on different NK subpopulations were assessed by flow cytometry. It was found that Tim-3 was expressed on all subpopulations of peripheral blood NK cells (CD16-CD56brightNK, CD16+CD56dimNK, CD16+CD56-NK). Incubation with galectin-9 increased the expression of Tim-3 on regulatory CD16-CD56brightNK cells and did not change on cytotoxic CD16+CD56dim/-NK cells. Galectin-9 reduced the percentage of cytotoxic CD16+CD56dimNK in culture, but did not influence the number of regulatory CD16-CD56bright NK and cytotoxic CD16+CD56-NK cells. Thus, galectin-9 regulates Tim-3 molecule expression and NK cell subpopulation distributions in vitro culture.

Galectin-3 and matrix metalloproteinases 2 and 9 in peripheral blood of gastric cancer patients

Background: High incidence of gastric cancer (GC), its aggressive clinical course, rapid tumor dissemination, low sensitivity to chemotherapy and lack of reliable laboratory diagnostic criteria urgently require a search for the most informative markers associated with key biologic properties of the tumors.
 Aim: Comparative analysis of galectin-3, matrix metalloproteinase (MMP)-2, and MMP-9 levels in peripheral blood of GC patients and healthy donors, assessment of association of these markers with clinical morphological characteristics of the disease, and prognosis of overall and relapse-free survival.
 Materials and methods: Sixty (60) primary treatment-nave GC patients (38 men, 22 women) aged 29 to 81 years and 90 healthy donors compatible with their age and sex were included into the study. Galectin-3 was measured in EDTA plasma, MMP-2 and MMP-9 in serum with standard direct enzyme immunoassay kits "Human MMP-2 (total)", "Human MMP-9 (total)", "Human Galectin-3" (RD Systems, USA).
 Results: Plasma galectin-3 concentration in the GC patients was significantly higher than in the healthy controls (median 12.9 and 10.6 ng/ml, respectively; p 0.0001). No difference in serum MMP-9 levels between GC patients and control subjects were found, while MMP-2 level in the control group was significantly higher, than in the GC patients (p = 0.039). No association between galectin-3, MMP-2, and MMP-9 blood levels in the GC patients could be identified. In contrast to GC patients, there was a positive correlation of plasma galectin-3 with age in the control group (rs = 0.51, p 0.005). No associations between the biomarkers levels in blood and clinical and morphological characteristics of GC were established, except MMP-9 being higher at Т4а invasion depth as compared to the earlier Т2 level. Marked differences in the overall survival depending on plasma galectin-3 levels were found, with the cut-off level of 12.9 ng/ml: the 5-year overall survival in the patients with low galectin-3 was better, than in those with its higher level (50 and 43%, respectively; however, the difference was non-significant, р 0.1). Both overall and relapse-free survival of the GC patients was higher in those with low ( 212 ng/ml) serum MMP-2: the 5-year overall survival in this group comprised 60% versus 23% in the patients with higher MMP-2 (p = 0.018). The difference in relapse-free survival was non-significant. Serum MMP-9 levels had no significant impact on the survival of GC patients.
 Conclusion: The ambiguous data on the clinical role of galectin-3, MMP-2, MMP-9 in GC obtained in this study indicate the necessity of further investigation of their possible utility for the diagnostics and prognosis of treatment results.

Galectin-3, a damage-associated molecular pattern, in tears of patients with vernal keratoconjunctivitis.

Galectin-3 is a damage-associated molecular pattern (DAMPs), released from damaged or dying cells. In this study, we investigated the concentration and source of galectin-3 in the tears of patients with vernal keratoconjunctivitis (VKC) and evaluated whether the concentration of galectin-3 in tears represents a biomarker of corneal epithelial damage. Clinical and experimental. We measured the concentration of galectin-3 in tear samples from 26 patients with VKC and 6 healthy controls by enzyme-linked immunosorbent assay (ELISA). The expression of galectin-3 in cultured human corneal epithelial cells (HCEs) stimulated with or without tryptase or chymase was investigated by polymerase chain reaction (PCR), ELISA, and Western blotting. We also estimated the concentration of galectin-3 in the supernatants of cultured HCEs induced to necrosis. Finally, we investigated whether recombinant galectin-3 induced the expression of various genes related to cell migration or the cell cycle in HCEs by using microarray analysis. High concentrations of galectin-3 were detected in the tears of patients with VKC. The concentration showed significant correlation with the severity of corneal epithelial damage. Stimulation of cultured HCEs with various concentrations of tryptase or chymase had no effect on the expression of galectin-3. However, high concentrations of galectin-3 were detected in the supernatants of necrotic HCEs. Recombinant human galectin-3 induced various cell migration- and cell cycle-related genes. The concentrations of galectin-3 in the tears of patients with VKC may represent a biomarker of the severity of corneal epithelial damage.

Value of NT-proBNP and Galectin-3 as Biomarkers in the Follow-Up of Asymptomatic Elderly Patients with Severe Aortic Stenosis.

Recognizing symptoms in elderly patients with severe aortic stenosis (AS) can be a challenge. Serum biomarkers such as Galectin-3 or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are involved in remodeling and heart failure (HF) development and could support the diagnosis of AS. We set out to test the usefulness of NT-proBNP and Galectin-3 in predicting events in this population. We designed a prospective observational case-control study, including 50 asymptomatic patients older than 70 years, diagnosed with severe degenerative AS, and 50 control individuals. The NT-proBNP and Galectin-3 levels were measured. A follow-up was carried out at 12 months to determine the occurrence of hospital admission for HF, all-cause mortality or the appearance of symptoms. The patients with severe AS had higher Galectin-3 and NT-proBNP concentrations. The area under the receiver operating characteristic curve of the NT-proBNP was 0.812 (95% CI, 0.646-0.832), and that of the Galectin-3 was 0.633 (95% CI, 0.711-0.913). NT-proBNP was a good predictor of events [HR 3.45 (95% CI 1.32-9.03), p = 0.011]. A Kaplan-Meier analysis showed that the probability of freedom from events was significant in patients who exhibited a combination of higher NT-proBNP and Galectin-3 levels (log-rank p = 0.032). Therefore, NT-proBNP was the most reliable predictor of events in asymptomatic patients with severe AS. A combination of NT-proBNP and Galectin-3 levels may be vital in the clinical follow-up of these patients and in the decision-making process.

Abstract P2-23-18: Analysis of Serum Galectin Profiles by Breast Cancer Subtypes and Patient Characteristics

Abstract Background: Galectins are sugar binding proteins that play a role in adhesion, apoptosis, immune regulation, and many other cellular processes. There are three different classes of galectins, and they are all found intracellularly and secreted in serum. Galectins have an established relationship with breast cancer, and galectin-3 has been repeatedly associated with cancer cell survival and tumor progression. Most research regarding breast cancer and galectins has used immunohistochemistry (IHC) as a method for identifying galectin expression in breast cancer tissue samples. However, little research has identified a relationship between serum galectin concentrations and breast cancer subtypes. Breast cancer is characterized both by histological and molecular subtype, and this identification often directs treatment decisions. The current method for identifying breast cancer subtypes is through invasive biopsy and the subsequent use of IHC. This project characterized serum galectin concentrations in breast cancer patients to determine if they changed based on different histological and molecular subtypes, cancer stage, and other patient characteristics. Our goal was to evaluate a potential noninvasive means of breast cancer subtype identification and to identify potential therapeutic targets. Methods: One-hundred breast cancer patient serum samples were studied using Enzyme-linked Immunosorbent Assays (ELISAs) to determine concentrations of galectins -1, -3, -7, and -9. Results were compared using many patient characteristics, including breast cancer subtype, stage, and patient history (smoking status and treatment). Statistical Analysis was performed using ANOVA, Student’s t-test, and the Wilcoxon Method. Results: The concentrations of galectins -1, -3, and -9 in breast cancer patients were all significantly higher than those of healthy controls (Table 1), which is consistent with previous studies. The concentration of galectin-3 was significantly higher in invasive lobular carcinoma samples (N, 6; mean, 13.04 ng/mL) compared to invasive ductal carcinoma samples (N, 80; mean, 9.93 ng/mL; p-value, 0.0428). Galectin-3 concentrations were significantly lower in samples from breast cancer patients who received chemotherapy (N, 9; mean, 9.22 ng/mL) versus those who did not (N, 7; mean, 14.60 ng/mL; p-value, 0.0228). Concentrations of galectin-1 were found to increase by stage (p-value, 0.0031), with significant differences between samples from patients with stage I breast cancer (N, 45; mean, 19.02 ng/mL) and both stage II (N, 40; mean, 24.15 ng/mL; p-value, 0.0127) and stage III (N, 12; mean, 28.37 ng/mL; p-value, 0.0026) disease. Conclusions: Our findings suggest a potential use for serum galectin-3 concentrations as a non-invasive means for breast cancer histological subtype differentiation and more refined diagnosis. In addition, our results suggest a possible use of galectin-1 concentrations for more accurate cancer staging. Further research could explore the relationship of serum galectin concentrations and other breast cancer subtypes. Future studies could also analyze how galectin concentrations change with patient treatment status and determine the potential of galectins as specific targets for breast cancer treatment. Table 1: Galectin Concentrations in Breast Cancer vs Healthy Controls Citation Format: Jonah Shealy, Alex Kesic, Avery Funkhouser, Julie Martin, W. Larry Gluck, w. Jeffery Edenfield, Anna Blenda. Analysis of Serum Galectin Profiles by Breast Cancer Subtypes and Patient Characteristics [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-18.

Plasma Galectin-3 Biomarkers in Chronic Kidney Disease

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

Effectiveness of Spironolactone in Terms of Galectin-3 Levels in Patients with Heart Failure with a Reduced Ejection Fraction in the Vietnamese Population.

Background: Galectin-3 is a biomarker that has been demonstrated to play a significant role in myocardial fibrosis and remodeling in the pathogenesis of heart failure. Furthermore, spironolactone has the ability to control galectin-3 levels in heart failure patients. Objectives: The aim of our study was to determine the factors associated with the increase in galectin-3 and the alteration of galectin-3 concentration in patients with heart failure with a reduced ejection fraction after 12 weeks of treatment with spironolactone. Materials and methods: A cross-sectional descriptive study was conducted on 122 patients with heart failure with a reduced ejection fraction. Those patients were nonusers of spironolactone and presented for examination or had been hospitalized at the Can Tho Cardiovascular Hospital in Vietnam. The demographic and cardiovascular risk factor details were obtained at baseline, and galectin-3 levels were measured at baseline and also 12 weeks after taking spironolactone 25 mg once daily vs. 50 mg once daily. Results: The median baseline galectin-3 was 54.82 ± 26.06. Galectin-3 levels were positively correlated with age, NT-proBNP, and negatively correlated between EF and galectin-3 levels (p < 0.05). After 12 weeks of treatment with spironolactone, the galectin-3 concentration decreased from 54.82 ± 26.06 to 44.20 ± 24.36 (p < 0.05). According to the subgroup analysis, the average concentration of galectin-3 decreased the most in the group of patients with grade 3 hypertension and NYHA class III heart failure. The 50 mg once-daily dose of spironolactone significantly improved galectin-3 concentrations compared with the 25 mg once-daily group, at 17.11 ± 20.81 (p < 0.05) (reduced 29.05%) and 3.46 ± 6.81 ng/mL (p < 0.05) (reduced 6.87%), respectively. Conclusion: Treatment with spironolactone played an essential role in reducing galectin-3 concentrations, especially spironolactone 50 mg once daily, which showed a significant effect on reducing galectin-3 compared with a 25 mg once-daily dose.

Circulating galectin-3 levels are inversely associated with subclinical cardiovascular disease in obese adults.

Galectin-3 is a new cytokine that is mainly secreted by activated macrophages. It is involved in apoptosis, inflammation and may play a role in the development of cardiovascular disease (CVD). However, there is little information about the association between circulating galectin-3 and subclinical atherosclerosis in humans. We measured serum galectin-3 in 483 obese adult subjects (aged 40years and over) who had the measurement of carotid intima-media thickness (CIMT) recruited from the community. Adults with lower levels of circulating galectin-3 had increased CIMT (p < 0.05). In multivariable linear regression analyses, circulating galectin-3 was independently associated with CIMT. The risks of increased CIMT were significantly decreased by 65.1% (OR (95% CI): 0.349 (0.165-0.739)), adjusting for possible confounding factors. Notably, individuals in the lowest quartile of serum galectin-3 were 1.80 times (p < 0.05) more likely to have increased CIMT than those in the highest quartile in multivariable logistic regression analyses; however, such associations with circulating galectin-3 were not noted for carotid plague. These findings propose that circulating galectin-3 concentrations are inversely associated with increased CIMT in obese adults, which may be a potential biomarker of CVD.

Evaluation of the Salivary Levels of Interleukin-17 and Galectin-3 in Patients with Periodontitis and Type 2 Diabetes Mellitus

Background: Periodontitis and type 2 diabetes mellitus are both considered as a chronic disease that affect many people and have an interrelationship in their pathogenesis. Objective: The aim is to evaluate the salivary levels of interleukin-17 (IL-17) and galectin-3 in patients with periodontitis and type-2 diabetes mellitus. Materials and Methods: The samples were gathered from 13 healthy (control group) and 75 patients split into 3 groups, 25 patients with type 2 diabetes mellitus and healthy periodontium (T2DM group), 25 patients with generalized periodontitis (P group), and 25 patients with generalized periodontitis and type 2 diabetes mellitus (P-T2DM group). Clinical periodontal parameters were documented. The concentration of IL-17 and galectin-3 in salivary samples was estimated using enzyme-linked immunosorbent assay. Result: The concentration of IL-17 in the T2DM group (388.612 ± 120.111 pg/mL), the P group (443.887 ± 69.188 pg/mL), and the P-T2DM group (532.769 ± 137.673 pg/mL) showed higher values than the control group (292.079 ± 62.356 pg/mL) with a significant difference at (P &lt; 0.05). Also, the P-T2DM group showed higher values than the P group and the T2DM group with a significant difference (P &lt; 0.05). The concentration of galectin-3 in the T2DM group (2.409 ± 0.147 ng/mL), the P group (2.699 ± 0.386 ng/mL), and the P-T2DM group (2.568 ± 0.285 ng/mL) showed higher values than the control group (1.888 ± 0.356 ng/mL) with a significant difference (P &lt; 0.05). The P group showed a higher value than the T2DM group with a significant difference (P &lt; 0.05). Conclusion: Salivary IL-17 and galectin-3 levels might be used as a biomarker for periodontitis.

THE ROLE OF NEUROHORMONAL FACTORS IN THE FORMATION OF A PATIENT’S CLINICAL PROFILE AND THE IMPACT ON STRUCTURAL CARDIAC AND VASCULAR REMODELING IN PATIENTS WITH MYOCARDIAL INFARCTION AFTER REPERFUSION THERAPY

The aim: To determine the dynamics of galectin-3 in the formation of the patient’s clinical profile and the impact on structural cardiac and vascular remodeling in patients with myocardial infarction after reperfusion therapy. Materials and methods: 140 patients with class II A CHF syndrome according to Vasilenko-Strazhesko FC II-III (NYHA), which occurred in patients with MI, and 22 patients with MI without signs of CHF were examined. Results: The average serum galectin-3 level of the studied patients was analyzed. The average concentration of galectin-3 in patients with stenting without signs of CHF was (10.87±1.65) ng/ml comparing to (6.57±0.21) ng/ml in healthy subjects (p&lt;0.05). An increase in the concentration of this indicator was observed in the group of patients with CHF after MI with reperfusion - (35.2±1.76) ng/ml, which is significantly higher in comparison with practically healthy subjects, and in patients without revascularization it was (38.94±1.97) ng/ml (p&lt;0.001). Positive correlations of medium strength were found between left ventricular end-systolic volume (ESV), left ventricular end-diastolic volume (LVEDV) and serum galectin-3 concentration in the examined patients. The correlation coefficient between the abovementioned indicators was 0.60 (p&lt;0.01) and 0.53 (p&lt;0.05), respectively. Conclusions: It has been determined that in patients with CHF with postinfarction cardiosclerosis there is a direct correlation of medium strength between the values of indicators of LV myocardial remodeling with plasma galectin-3 concentration, including ESV, EDV, in examined patients. The role of galectin-3 as a marker of postinfarction remodeling in patients with CHF for early diagnosis, prognosis, and risk stratification has been presented.

Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event.

Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 &gt; 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05-0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3-59.4] ng/mL vs. 18.9 [14.5-23.4] ng/mL, p &lt; 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.

Plasma levels of galectin-3 in residents of the Podillya region of Ukraine without signs of cardiovascular pathology carriers of different variants of the coding gene (LGALS-3, rs 2274273)

Annotation. The purpose of the study is to investigate the plasma level of galectin-3 in postmenopausal women without signs of cardiovascular pathology and its possible association with the structural and functional parameters of the myocardium in carriers of different polymorphic variants of the coding gene (LGALS-3, rs2274273). 67 women of postmenopausal age (average age 56.43±0.64 years) without signs of cardiovascular pathology residents of the Podillya region of Ukraine were examined. In addition to the general clinical examination, the research used the enzyme immunoassay method to determine the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene at the rs2274273 locus by means of polymerase chain reaction, and ultrasound of the heart. Statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. By means of correlation analysis with the calculation of Spearman's rank correlation coefficients (r), an assessment of the possible association of the plasma level of the biomarker and the structural and functional indicators of the heart was carried out. The critical value of the significance level (p) was ≤0.05. In the examined population of women, there was no significant difference between the frequency of occurrence of the GA and GG genotypes carriers of the galectin-3 gene locus rs2274273: 49.25% (n=33) and 40.30% (n=27), respectively (p&gt;0.05). The AA genotype variant was found in 10.45% (n=7) of individuals, which is significantly less frequent than both the GA and GG genotypes (p&lt;0.01). The frequency of distribution of genotypes corresponded to the Hardy-Weinberg equilibrium. The average level of galletin-3 in blood plasma in women was 6.68±0.30 ng/ml, it was within the generally accepted norms and did not reliably differ from the corresponding indicators in men of the same region. No significant difference in plasma concentrations of galectin-3 was found in carriers of different polymorphic variants of the galectin-3 gene. Correlation between the level of galectin-3 in the blood plasma and most indicators of intracardiac and systemic hemodynamics in women without cardiovascular pathology was not found. In the future, it is planned to study the formation of prerequisites for chronic heart failure (CHF) in women with EH based on indicators of the plasma level of galectin-3 in carriers of polymorphic variants of the coding gene (LGALS-3, rs2274273).

Evaluation of IL-33R and Galectin-3 as New Biomarkers of Cardiac Damage after Polytrauma-Association with Cardiac Comorbidities and Risk Factors.

Polytrauma is one of the disorders with the greatest economic impact on healthcare in society and one predictor for poor outcome is cardiac damage. Interleukin 33 receptors (IL-33R) and galectin-3 are two new potential cardiac trauma biomarkers that are the subjects of this investigation. Additionally, this study assesses pre-existing cardiac damage or risk factors as predictors of cardiac damage after polytrauma. This retrospective study includes 107 polytraumatized patients with an ISS ≥16 admitted in a Level 1 Trauma Centre. Plasma samples were taken at admission. IL-33R and galectin-3 concentrations were detected in plasma samples by ELISA. Both did not correlate with the cardiac damage measured by troponin. Next to troponin, IL-33R was increased in patients with pre-existing cardiac comorbidities. In the subgroup of patients with cardiac comorbidities, the BMI and the initial blood sugar level were significantly increased compared to patients without cardiac comorbidities. Galectin-3 and IL-33R were shown to not correlate with cardiac damage. However, our data suggests that IL-33R protein should be revised in future studies as a marker of cardiac comorbidities. Further, our data indicate that patients with cardiac comorbidities represent a separate group of polytrauma patients characterized by higher concentrations of troponin, IL-33R, BMI and initial sugar level.

Galectin-1 and Galectin-9 Concentration in Maternal Serum: Implications in Pregnancies Complicated with Preterm Prelabor Rupture of Membranes

Preterm prelabor rupture of membranes (pPROM) accounts for nearly half of premature births. Although several risk factors have been identified, no markers allowing for effective prevention have been discovered. In this study, we investigated how the maternal serum levels of galectin-1 and galectin-9 change in patients with pPROM in comparison to uncomplicated pregnancies. A total of 75 patients were enrolled to both study and control group (37 vs. 38, respectively). The serum concentration of galectin-1 and galectin-9 were assayed in duplicate using an enzyme-linked immunoassay. All analyses were performed using PQ Stat v. 1.8.4 software. Galectin-1 levels were significantly higher in the controls (13.32 vs. 14.71 ng/mL, p = 0.02). Galectin-9 levels were similar in both groups (13.31 vs. 14.76 ng/mL, p = 0.30). Lower galectin levels were detected for early pPROM (before 32nd GW) in comparison to late pPROM and the controls (8.85 vs. 14.45 vs. 14.71 ng/mL, p = 0.0004). Similar trend was observed in galectin-9 levels, although no statistical significance was found (11.57 vs. 14.25 vs. 14.76 ng/mL, p = 0.26). Low galectin-1 maternal serum level is associated with the incidence of preterm prelabor rupture of membranes. Galectin-9 maternal serum levels were not significantly correlated with pPROM. However, in order to investigate gal-1 and gal-9 levels as potential, promising markers of pPROM, further clinical studies on larger groups are required.

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p < 0.001). Conventional RV longitudinal and global function parameters (S′, fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p < 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process—increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.

DYNAMICS OF GALECTIN-3 LEVELS IN PATIENTS WITH ACUTE CORONARY SYNDROMES AND 2 TYPE DIABETES MELLITUS UNDER THE INFLUENCE OF EMPAGLIFLOZIN AND TRIMETAZIDINE

It is known that cardiovascular diseases (CVD) will continue to occupy a prominent place in the structure of morbidity, mortality and disability of the world population. Patients with diabetes (DM) are several times more likely to develop adverse cardiovascular events. In recent years, markers of inflammation, which are involved in the progression of atherosclerosis, have been studied. One of them is galectin-3, which is involved in cell differentiation, fibrosis and immune inflammation. Data on changes in the activity of galectin-3 concentration in patients with ACS are scarce and contradictory.&#x0D; The purpose is to study the dynamics of galectin-3 content in the blood of patients with acute coronary syndromes (ACS) and concomitant type 2 diabetes in the course of treatment using empagliflozin and trimetazidine.&#x0D; Material and methods. At the first stage, 124 patients with ACS were examined; the control group consisted of 30 practically healthy people. The second stage of the study included 93 patients with ACS and diabetes, who, depending on the treatment strategy, were divided into 3 subgroups: 29 patients who were prescribed therapy in accordance with the guidelines; 30 patients who were additionally prescribed empagliflozin at a dose of 10 mg per day; 34 patients were prescribed a combination of empagliflozin and trimetazidine at a dose of 35 mg twice a day in addition to optimal drug therapy. All patients were examined upon admission before starting the course of treatment. Repeated examinations were carried out on the 28th day and after 3 months. Galectin-3 content was determined by enzyme- linked immunosorbent assay (ELISA). General laboratory tests were carried out, as well as determination of blood levels of brain natriuretic peptide (NT - proBNP), highly sensitive C-reactive protein (hs CRP), glycosylated hemoglobin. The severity of coronary artery damage was calculated according to the Gensini scale. Statistical processing received data were collected using the standard package of the "Statistics 12" program. The data were considered reliable at p &lt;0.05.&#x0D; Research results. The average age of the examined patients was (63.4 ± 5.21) years. The average values of galectin-3 levels in the blood of patients with ACS without type 2 diabetes were: (28.23 ± 3.17) ng /ml, and with concomitant DM – (35.67 ± 2.98) ng /ml (p &lt;0.01), which was 3.18 and 4.01 times higher indicators of control groups : (8.89 ± 3.41) ng /ml, respectively (p &lt;0.001).&#x0D; By the multivariate method regressive linear modeling noted dependence between levels of galectin-3 in patients with ACS with type DM and the number of leukocytes, levels hsCRP, NT- proBNP, creatinine, glucose, glycosylated hemoglobin and severity of coronary artery damage due to the Gensini scale.&#x0D; At the end of study, on the 28th day, a significant decrease in the content of galectin-3 in the blood was observed only in the group of patients who were additionally prescribed a combination of empagliflozin and trimetazidine - by 22.13% of the initial values. At the end of observation (3rd month) in all groups of examined patients, the average values of the specified indicator decreased to the same extent, however, they did not return to normal values.&#x0D; Conclusions:&#x0D; &#x0D; Concomitant type 2 diabetes significantly affects the increase of galectin-3 levels in the blood of patients with acute coronary syndrome.&#x0D; The additional appointment of trimetazidine leads to a faster decrease in the levels of galectin-3 in the blood of patients.&#x0D;

Serum Galectin-3 and Mucin-1 (CA15-3) in Relation to Renal Function in Untreated Chinese Patients.

Galectin-3 is a multi-functional lectin protein and a ligand of mucin-1 (CA15-3), and has been linked to renal fibrosis in animal models and renal function in humans. However, no population study has ever explored the associations with both ligand and receptor. We therefore investigate the independent association of renal function with serum galectin-3 and mucin-1 (CA15-3) in untreated Chinese patients. The study participants were outpatients who were suspected of hypertension, but had not been treated with antihypertensive medication. Serum galectin-3 and mucin-1 (CA15-3) concentrations were both measured by the enzyme-linked immunosorbent assay (ELISA) method. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine by the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The 1,789 participants included 848 (47.4%) men. Mean (±SD) age was 51.3 ± 10.7 years. Multiple regression analyses showed that eGFR was significantly associated with serum galectin-3 and mucin-1 (CA15-3) concentration (0.68 and 1.32 ml/min/1.73 m2 decrease per 1-SD increase in log transformed serum galectin-3 and mucin-1 (CA15-3) concentration, respectively; P ≤ 0.006). The association of eGFR with serum mucin-1 (CA15-3) concentration was significantly stronger in the overweight (BMI 24.0-27.9 kg/m2) and obese (BMI ≥ 28.0 kg/m2) than in normal weight subjects (BMI < 24.0 kg/m2, P for interaction 0.018). Path analysis showed that serum galectin-3 concentration had both a direct (P = 0.016) and a mucin-1 mediated indirect effect (P = 0.014) on eGFR. Both circulating galectin-3 and mucin-1 (CA15-3) were significantly associated with renal function. The role of galectin-3 on renal function might be partially via mucin-1.

Measurement of Plasma Galectin-3 Concentrations in Patients with Catheter Infections: A Post Hoc Retrospective Cohort Study.

Catheter-related infections (CRIs) include catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), and they are associated with high morbidity, mortality, and healthcare costs. The diagnosis of a CRI is made difficult by its non-specific symptoms. We aimed to investigate the factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for CRIs. Circulating the concentrations of galectin-3, we measured the chemokine (C-C) motif ligand 2, procalcitonin, and C-reactive protein in 110 patients with a central catheter, in 165 patients with a urinary catheter, and in 72 control subjects. Catheter-bearing patients had higher concentrations (p < 0.001) of galectin-3 than the control group [central catheter: 19.1 (14.0–23.4) µg/L; urinary catheter: 17.1 (12.7–25.4) µg/L; control group: 6.1 (5.0–8.7) µg/L]. We identified chronic kidney disease as an independent determinant of galectin-3 concentrations in patients with a central catheter, and serum creatinine, cardiovascular disease, and number of days that the catheter was indwelling were identified as determinants in urinary catheter patients. We found that measuring galectin-3 concentrations in urinary catheter patients with a CRI was more accurate for diagnosis than the other parameters. We conclude that the measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of CRIs in those with a urinary catheter.