1. Introduction:

Galectin-3 is a member of the galectins family of carbohydrate-binding proteins with specificity for N-acetyllactosamine (LacNAc)-containing glycoproteins, and the only known one with a single carbohydrate recognition domain and a unique N-terminus ^[1][2]. It is a 30 kDa molecule encoded by the LGALS3 gene that is located on chromosome 14, locus q21–q22 ^[3]. It is mainly secreted by macrophages and regulates basic cellular functions including growth, proliferation, differentiation and inflammation ^[4][5][6][7] and importantly has been found to play a role in cardiac fibrosis ^[8][9].  Studies have suggested that galectin-3 can help to predict prognosis of heart failure and adverse events in various clinical settings such as patients with ST elevation myocardial infraction ^[10], congenital heart disease patients with a Fontan circulation ^[11] and survivors of out-of-hospital cardiac arrest ^[12]. In addition, its levels have been correlated with morbidity and mortality in patients with heart failure ^{[13][14][15][16]}.

Galectin-3 is a member of the galectins family of carbohydrate-binding proteins with specificity for N-acetyllactosamine (LacNAc)-containing glycoproteins, and the only known one with a single carbohydrate recognition domain and a unique N-terminus [1,2]. It is a 30 kDa molecule encoded by the LGALS3 gene that is located on chromosome 14, locus q21–q22 [3]. It is mainly secreted by macrophages and regulates basic cellular functions including growth, proliferation, differentiation and inflammation [4,5,,6,7] and importantly has been found to play a role in cardiac fibrosis [8,9].  Studies have suggested that galectin-3 can help to predict prognosis of heart failure and adverse events in various clinical settings such as patients with ST elevation myocardial infraction [10], congenital heart disease patients with a Fontan circulation [11] and survivors of out-of-hospital cardiac arrest [12]. In addition, its levels have been correlated with morbidity and mortality in patients with heart failure [13,14,15,16].

2. Possible mechanism of galectin 3 in heart failure

In response to cardiac injury, activated macrophages produce galectin-3 which is then thought to regulate phenotypic change of cardiac fibroblasts from the resting to the activated status [17], whereas sST2 binds to IL33 to block the binding of IL33 to ST2 on cardiomyocytes. Binding of IL33 to cardiomyocyte membrane ST2 results in the initiation of IL33/ST2 pathway which then evokes an antihypertrophic and antifibrotic function [18].

Schematic of possible mechanism of galectin 3 in heart failure

3. Application of galectin-3 in adult and pediatric patients with heart failure requiring ECLS

Application of galectin-3 in adult and pediatric patients with heart failure requiring ECLS

Heart failure is a life-threatening condition in both adults and children and is associated with high mortality, morbidity, and cost of care. Extracorporeal life support (ECLS) including ventricular assist device (VAD) implantation and extracorporeal membrane oxygenation (ECMO) is required for patients with advanced or end-staged heart failure either as destination therapy or as a bridge-to-transplantation therapy. Galectin-3 is one of biomarkers that has been employed in attempt to predict these outcomes in adult and pediatric patients with heart failure requiring ECLS, but there is significantly less literature regarding galectin-3 in pediatric patients as compared to adults, as shown in Table below. Higher values (>15.3 ng/mL) of galectin-3 have been reported to show a correlation with the severity of heart failure [19].

Perspective

Extracorporeal life support (ECLS) including ventricular assist device (VAD) implantation and extracorporeal membrane oxygenation (ECMO) is required for patients with advanced or end-staged heart failure either as destination therapy or as a bridge-to-transplantation. Undergoing ECLS creates a complex clinical situation with challenges related to early and accurate prediction of prognosis, particularly in pediatric patients. To distinguish patients, who will improve and those who will not early during ECLS, is imperative as it would not only assist the medical team to formulate an optimal care plan but may also provide a scientific justification to initiate ethical discussions with the patient’s family. Galectin 3 along with other biomarkers, for instance, sST2, have been documented as prognostic markers for myocardial recovery in patients with refractory heart failure requiring circulatory support. However, neither galectin-3 and/or sST2 has been examined as guides for adjusting medical management for heart failure in pediatric patients, and thus the role of galectin-3 and /or sST2 as a guide to therapeutic decision-making remains to be established.

4. Perspective

References

Extracorporeal life support (ECLS) including ventricular assist device (VAD) implantation and extracorporeal membrane oxygenation (ECMO) is required for patients with advanced or end-staged heart failure either as destination therapy or as a bridge-to-transplantation. Undergoing ECLS creates a complex clinical situation with challenges related to early and accurate prediction of prognosis, particularly in pediatric patients. To distinguish patients, who will improve and those who will not early during ECLS, is imperative as it would not only assist the medical team to formulate an optimal care plan but may also provide a scientific justification to initiate ethical discussions with the patient’s family. Galectin 3 along with other biomarkers, for instance, sST2, have been documented as prognostic markers for myocardial recovery in patients with refractory heart failure requiring circulatory support. However, neither galectin-3 and/or sST2 has been examined as guides for adjusting medical management for heart failure in pediatric patients, and thus the role of galectin-3 and /or sST2 as a guide to therapeutic decision-making remains to be established.

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