Galectin‐3 enhances Atrial Remodeling and Arrhythmogenesis through CD98 Signaling

Introduction: Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse.Aim: The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role.Materials and methods: We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment.Results: Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs.Conclusions: Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.

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

Journal of Investigative Medicine ◽

10.1136/jim-2020-001459 ◽

2020 ◽

Vol 69 (1) ◽

pp. 20-27

Author(s):

Gokhan Aksan ◽

Ahmet Yanık ◽

Osman Can Yontar ◽

Ömer Gedikli ◽

Ugur Arslan ◽

...

Keyword(s):

Cardiac Resynchronization Therapy ◽

Electronic Device ◽

Multivariate Logistic Regression Analysis ◽

High Rate ◽

Cardiac Resynchronization ◽

Atrial Remodeling ◽

Resynchronization Therapy ◽

Galectin 3 ◽

Long Term Follow Up

Galectin-3 is an inflammation biomarker associated with atrial remodeling which plays a role in the development of atrial fibrillation (AF). Atrial high-rate episode (AHRE) is related to development of clinically documented AF and stroke. The present study aimed to determine the relationship between the presence of AHRE and the coronary sinus (CS) serum sampling of galectin-3 levels in the long-term follow-up of cardiac resynchronization therapy (CRT) patients. A total of 108 consecutive CRT patients were included prospectively in the study. AHREs were defined as atrial tachyarrhythmia episodes lasting at least 6 min with atrial rate >190 beats/min detected by cardiac implantable electronic device. CS blood samples were drawn from the CS guiding catheter to perform galectin-3 measurements. Galectin-3 levels were measured via ELISA. During a mean follow-up 12.6±4.9 months, AHRE was observed in 31 (28.7%) patients and not observed in 77 (72.3%) patients. CS galectin-3 levels were significantly higher in patients with AHRE than those without AHRE (18.09±2.62 vs 13.17±3.17, respectively, p<0.001). Moreover, CS galectin-3 levels showed significant positive correlation with percent of time spent in total AHRE (r=0.436, p<0.001). Multivariate logistic regression analysis demonstrated that left atrium (LA) volume and CS galectin-3 levels were significant and independent predictors for AHRE (OR=1.127, 95% CI: 1.045 to 1.216; p=0.002, OR=1.799, 95% CI: 1.388 to 2.330; p<0.001, respectively). In this study, we determined that high CS galectin-3 levels were a predictor for the development of AHRE in CRT patients.

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Role of NLRP3-Inflammasome/Caspase-1/Galectin-3 Pathway on Atrial Remodeling in Diabetic Rabbits

Journal of Cardiovascular Translational Research ◽

10.1007/s12265-020-09965-8 ◽

2020 ◽

Vol 13 (5) ◽

pp. 731-740 ◽

Cited By ~ 2

Author(s):

Xiaohan Wu ◽

Yang Liu ◽

Daimiao Tu ◽

Xianjian Liu ◽

Shulin Niu ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Atrial Remodeling ◽

Caspase 1 ◽

Galectin 3 ◽

Diabetic Rabbits

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Galectin-3 in Heart Failure with Preserved Ejection Fraction and Persistent Atrial Fibrillation Versus Sinus Rhythm. Correlation with Left Atrial Volume and N-Terminal Pro B-Type Natriuretic Peptide

Journal of Cardiovascular Disorders ◽

10.26420/jcardiovascdisord.2021.1043 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Bertoni M ◽

◽

Traini AM ◽

Celli A ◽

Bini C ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Left Atrial ◽

Independent Predictor ◽

Left Atrial Volume ◽

Atrial Remodeling ◽

Preserved Ejection Fraction ◽

Atrial Volume ◽

Left Atrial Remodeling ◽

Galectin 3

Background: Galectin-3 (Gal-3) is considered both a profibrotic biomarker in Heart Failure with preserved Ejection Fraction (HFpEF) and a biomarker of atrial remodeling in Atrial Fibrillation (AF). The Left Atrial Volume Index (LAVI) is an echocardiographic parameter considered an index of left atrial remodeling. Aim of this study was to analyse the relation of Gal-3 levels with both LAVI and N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) in patients with HFpEF and Persistent AF (HFpEF-PAF). Methods: Serum Gal-3 and NT-proBNP, along with LAVI were measured. A comparison of such parameters between 49 patients with HFpEF-PAF and 53 patients with HFpEF and sinus rhythm (HEpEF-SR) was made. Results: Galectin-3, NT-proBNP and LAVI were significantly higher in patients with HFpEF-PAF compared to HFpEF-SR (23±7 ng/mL vs 19.5±8.5 ng/mL, p=0.027; 3,406.8±2,321.9 pg/mL vs 1,459.6±1,372 pg/mL, p<0.001; 40.1±11mL/m² vs 28.4±7.7 mL/m², p<0.001, respectively). In HFpEF-PAF, Gal- 3 showed a significant correlation with both NT-proBNP (r=0.40, p=0.0038) and LAVI (r=0.28, p=0.044). We found a significant association between patients with higher levels of Gal-3 >17.8 ng/mL and HFpEF-PAF (p=0.002). Finally, a multivariate logistic regression analysis adjusted for age, sex and traditional clinical AF risk factors showed that Gal-3 >17,8 ng/mL (OR 3.862, 95% CI 1.416 to 10.532, p=0.008) was an independent predictor of PAF. Conclusions: In patients with HFpEF-PAF Gal-3 was higher and related with both NT-proBNP and LAVI. The latter correlation may be relevant because LAVI is considered an index of left atrial remodeling. Moreover, higher levels of Gal-3>17,8 ng/mL were an independent predictor of PAF.

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Analysis of the Correlation of Galectin-3 Concentration with the Measurements of Echocardiographic Parameters Assessing Left Atrial Remodeling and Function in Patients with Persistent Atrial Fibrillation

Biomolecules ◽

10.3390/biom11081108 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1108

Author(s):

Paweł Wałek ◽

Urszula Grabowska ◽

Elżbieta Cieśla ◽

Janusz Sielski ◽

Joanna Roskal-Wałek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Systolic Function ◽

Persistent Atrial Fibrillation ◽

Atrial Remodeling ◽

Left Atrial Wall ◽

Galectin 3 ◽

Echocardiographic Parameters ◽

Fibrosis Marker ◽

And Function

Galectin-3 (gal-3) is a fibrosis marker and may play a role in fibrosis of the left atrium (LA). Left atrial wall fibrosis may influence the transition from paroxysmal to non-paroxysmal atrial fibrillation (AF). In this study, we assessed the correlation of gal-3 concentration with the main echocardio-graphic parameters evaluating dimensions, volume, compliance, and left atrial contractility during AF and after successful electrical cardioversion (DCCV). The study included 63 patients with left atrial enlargement who qualified for DCCV due to persistent AF. The procedure recovered sinus rhythm in 43 (68.3%) patients. The concentration of gal-3 was negatively correlated with the echocardiographic parameters of LA including dimensions (LA length pre, rho = −0.38; p = 0.003), volume (LAV pre, rho = −0.39; p = 0.003), compliance (LASr mean post, rho = −0.33) and contractility (pLASRct mean post, rho = −0.33; p = 0.038). Negative correlations of gal-3 concentration were also observed in relation to the volume and contractility of the left ventricle. The concentration of gal-3 significantly negatively correlates with the size, systolic function, and compliance of the LA wall in patients with persistent AF. Determining gal-3 concentration in patients with persistent AF may help in the assessment of remodeling of the LA wall.

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miR−21 and NT-proBNP Correlate with Echocardiographic Parameters of Atrial Dysfunction and Predict Atrial Fibrillation

Journal of Clinical Medicine ◽

10.3390/jcm9041118 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1118

Author(s):

Jan-Thorben Sieweke ◽

Tobias Jonathan Pfeffer ◽

Saskia Biber ◽

Shambhabi Chatterjee ◽

Karin Weissenborn ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Left Atrial ◽

Area Under The Curve ◽

Serum Biomarkers ◽

Atrial Remodeling ◽

Circulating Biomarkers ◽

Atrial Remodelling ◽

Galectin 3 ◽

Echocardiographic Parameters

This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin−3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)−21, −29a, −133a, −146b and −328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR−21 (r = −0.277, p = 0.012), miR−29a (r = −0.269, p = 0.015), miR−146b (r = −0.319, p = 0.004) and miR−328 (r = −0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a’: r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR−21 and NT-proBNP as predictive markers for AF (miR−21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04–0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001–1.004, p = 0.006). Combination of NT-proBNP and miR−21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR−21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined.

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Galectin-3 in Atrial Fibrillation: A Novel Marker of Atrial Remodeling or Just Bystander?

The American Journal of Cardiology ◽

10.1016/j.amjcard.2015.03.055 ◽

2015 ◽

Vol 116 (1) ◽

pp. 163 ◽

Cited By ~ 5

Author(s):

Jelena Kornej ◽

Josephin Schmidl ◽

Andreas Bollmann

Keyword(s):

Atrial Fibrillation ◽

Atrial Remodeling ◽

Galectin 3

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Protective role of peroxiredoxin-4 in heart failure

Clinical Science ◽

10.1042/cs20191072 ◽

2020 ◽

Vol 134 (1) ◽

pp. 71-72

Author(s):

Naseer Ahmed ◽

Masooma Naseem ◽

Javeria Farooq

Keyword(s):

Heart Failure ◽

Cardiac Fibroblasts ◽

Protective Role ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Total Antioxidant ◽

Galectin 3 ◽

Consequent Increase ◽

And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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