Easily Multiplexable Immunoplatform to Assist Heart Failure Diagnosis through Amperometric Determination of Galectin‐3 (original) (raw)
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The Utility of Galectin-3 as a Diagnostics and Pharmacotherapy Monitoring Biomarker in Heart Failure
The Utility of Galectin-3 as a Diagnostics and Pharmacotherapy Monitoring Biomarker in Heart Failure, 2019
Development of new biomarkers, which can be used as instruments for early detection of diseases to select drug therapy and monitor its efficacy, is of great importance. The aim of this work is to assess the serum galectin-3 and N-terminal-pro brain natriuretic peptide (NT-proBNP) changes after 3 weeks of standard heart failure pharmacotherapy. Materials and Methods: The study included 65 patients (38 women and 27 men) with New York Heart Association II-III chronic heart failure. Mean age of patients was 71.2 ± 10.4 years. According to echocardiographic study, the patients were divided into two groups: the first group (HFpEF) included patients with ejection fraction < 55% and the second group (HFrEF) consisted of patients with ejection fraction > 55%. Median baseline NT-proBNP levels were 47.5 [IQR, 27.2; 76.4] and 99.0 [IQR, 45.6; 160.2] pmol/l in HFpEF and HFrEF groups, respectively. Median baseline galectin-3 levels were 8.0 [5.4; 10.8] ng/ml in HFpEF group, and 9.7 [7.7; 16.1] ng/ml in HFrEF group. Results: The correlation between the increased galectin-3 level and ejection fraction (r =-0.3; p = 0.04), creatinine (r = 0.3, p = 0.04), and increased plasma NT-proBNP (r = 0.3; p = 0.02) was found. By the end of the third week of the treatment period, galectin-3 levels decreased from 8.0 [IQR 5.4; 10.8] ng/ml to 6.3 [IQR 3.4; 8.7] ng/ml in HFpEF group, and from 9.7 [7.7; 16.1] ng/ml to 7.1 [5.3; 12.8] ng/ml in HFrEF group. Conclusion: Galectin-3 can be considered as a useful biomarker for heart failure diagnostics and pharmacotherapy monitoring.
Galectin-3: a potential biomarker for diagnostics of heart failure
2018
Heart failure is a dysfunction with varied ethology; one of possible causes is anticancer treatment with anthracyclines. Rapid diagnosis is important because the disease is associated with high mortality and morbidity. The only biomarkers fully approved for diagnostics of heart failure are natriuretic peptides. They are secreted by ventricular muscle cells in response to volume and pressure overload. However, their concentration can be influenced by other factors, such as age or gender. A potential marker, not affected by these issues might be galectin-3. Current studies showed that galectin can play particularly significant role in myocardial fibrosis and inflammation. Elevated galectin-3 concentration has been observed in such cardiovascular diseases as heart failure, atherosclerosis, stroke and myocardial infarction. The review summarizes results of studies which indicate the role of galectin-3 in inducing fibrosis and cardiac remodelling (processes which influence disease progr...
ACS applied materials & interfaces, 2018
We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (Gal3), using the anti-Gal3 antibody as a biorecognition element and surface plasmon resonance (SPR) for transducing the bioaffinity event. The immunosensing platform was built at a thiolated Au surface modified by self-assembling four bilayers of poly(diallyldimethylammonium chloride) and graphene oxide (GO), followed by the covalent attachment of 3-aminephenylboronic acid (3ABA). The importance of GO, both as the anchoring point of the antibody and as a field enhancer for improving the biosensor sensitivity, was critically discussed. The advantages of using 3ABA to orientate the anti-Gal3 antibody through the selective link to the Fc region were also demonstrated. The new platform represents an interesting alternative for the label-free biosensing of Gal3 in the whole range of clinically relevant concentrations (linear range between 10.0 and 50.0 ng mL, detection limit of 2.0 ng mL) wit...
Scientific Reports
Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that binds to glycoproteins thereby regulating their activities 1. Clinical studies have shown that high circulating Gal-3 levels are indicative of severity of heart diseases or associated with increased risk of major adverse cardiovascular events including heart failure (HF) 2 , arrhythmias 3-5 , arterial stiffening 6 , re-hospitalization post-HF discharge 7 , diastolic dysfunction 8 , severity of atrial fibrosis 5,9 or mortality 10,11. However, a lack of association of Gal-3 levels and disease severity has also been reported in some studies 12-15. The mechanism(s) responsible for increased blood levels of Gal-3 remains incompletely defined. While increased cardiac Gal-3 expression was observed in human cardiac biopsies 5,9,16,17 , cardiac release of Gal-3 is not evident in patients with atrial fibrillation or severe HF indicated by the absence of a trans-cardiac Gal-3 gradient 18,19. A positive correlation between blood and myocardial levels of Gal-3 was reported in one study 20 , but not in another study 16. Clinical studies have consistently reported a strong and negative correlation between circulating Gal-3 levels and estimated glomerular filtration rate (eGFR), indicating that renal dysfunction is a determinant of blood Gal-3 levels 13,21-23. Indeed, Gal-3 levels are markedly elevated in patients with end-stage renal failure 24 .
Procedia Engineering, 2014
In this present study, a fully integrated BioMEMS was developed using silicon technology to simultaneously detect varying cytokine biomarkers: interleukin-1 (IL-1), interleukin-10 (IL-10), and interleukin-6 (IL-6) using eight gold working microelectrodes (WE). The biomarkers are one of many antigens that are secreted in acute stages of inflammation after left ventricle assisted device (LVAD) implantation for patients suffering from heart failure (HF). The monoclonal antibodies (mAb): anti-human IL-1, IL-10, and IL-6 were immobilized onto gold microelectrodes through functionalization with carboxyl diazonium, respectively. Cyclic voltammetry (CV) was applied during the microelectrode functionalization process to characterize the gold microelectrode surface properties, while electrochemical impedance spectroscopy (EIS) was used to characterize the modified gold microelectrodes. The BioMEMS was highly sensitive towards the three cytokines in a range of 1 pg/mL to 15 pg/mL, which is the window where acute inflammations were observed.
Prognostic Value of Serial Galectin-3 Measurements in Patients With Acute Heart Failure
Journal of the American Heart Association, 2017
Several clinical studies have evaluated the association between galectin-3 levels and outcome in patients with heart failure (HF). However, little is known about the predictive value of repeated galectin-3 measurements. This study evaluates the prognostic value of repeated time-dependent galectin-3 measurements in acute HF patients. In the TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients with Heart Failure) clinical cohort study, 496 acute HF patients were enrolled in 14 hospitals in The Netherlands, between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. Associations between repeated biomarker measurements and the primary end point were assessed using a joint model. Median age was 74 years and 37% were women. The primary end point, composite of all-cause mortality and HF rehospitalization, was reached in 188 patients (40%), during a median follow-up of 325 days (interquartile range 85-401). The median baseline...
Labeling galectin-3 for the assessment of myocardial infarction in rats
EJNMMI Research, 2014
Background: Galectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF). It is an established biomarker associated with extracellular matrix (ECM) turnover during myocardial remodeling. The aim of this study is to test the ability of 123 I-galectin-3 (IG3) to assess cardiac remodeling in a model of myocardial infarction (MI) using imaging techniques. Methods: Recombinant galectin-3 was labeled with iodine-123 and in vitro binding assays were conducted to test 123 I-galectin-3 ability to bind to ECM targets. For in vivo studies, a rat model of induced-MI was used. Animals were subjected to magnetic resonance and micro-SPETC/micro-CT imaging two (2 W-MI) or four (4 W-MI) weeks after MI. Sham rats were used as controls. Pharmacokinetic, biodistribution, and histological studies were also performed after intravenous administration of IG3. Results: In vitro studies revealed that IG3 shows higher binding affinity (measured as counts per minute, cpm) (p < 0.05) to laminin (2.45 ± 1.67 cpm), fibronectin (4.72 ± 1.95 cpm), and collagen type I (1.88 ± 0.53 cpm) compared to bovine serum albumin (BSA) (0.88 ± 0.31 cpm). Myocardial quantitative IG3 uptake (%ID/g) was higher (p < 0.01) in the infarct of 2 W-MI rats (0.15 ± 0.04%) compared to control (0.05 ± 0.03%). IG3 infarct uptake correlates with the extent of scar (r s = 1, p = 0.017). Total collagen deposition in the infarct (percentage area) was higher (p < 0.0001) at 2 W-MI (24.2 ± 5.1%) and 4 W-MI (30.4 ± 7.5%) compared to control (1.9 ± 1.1%). However, thick collagen content in the infarct (square micrometer stained) was higher at 4 W-MI (20.5 ± 11.2 μm 2) compared to control (4.7 ± 2.0 μm 2 , p < 0.001) and 2 W-MI (10.6 ± 5.1 μm 2 , p < 0.05). Conclusions: This study shows, although preliminary, enough data to consider IG3 as a potential contrast agent for imaging of myocardial interstitial changes in rats after MI. Labeling strategies need to be sought to improve in vivo IG3 imaging, and if proven, galectin-3 might be used as an imaging tool for the assessment and treatment of MI patients.