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Published online: 2025-02-25

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Galectin-3: Heart failure biomarker in pediatric heart defects

Daniel Gondko1, Patrycja Dębiec1, Jakub Roman1, Nikodem Pietrzak1, Krzysztof Kocot1, Jacek Kusa1
Pubmed: 39998403

Abstract

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has emerged as a potential diagnostic and prognostic biomarker for various diseases, including certain heart and kidney diseases, as well as cancer. Its significance is particularly notable in the context of congenital heart defects (CHD), which are the most prevalent congenital malformations, occurring in 6 to 8 out of every 1000 live births. Symptoms of heart failure (HF) in patients with congenital heart defects can manifest early in life, but in some cases, the disease progresses gradually, leading to a gradual decline in quality of life and the development of various complications. This variability underscores the need for early biomarkers to detect HF development in pediatric patients. Gal-3 plays a key role in myocardial remodeling, making it a promising candidate for advancing the diagnosis and management of HF in CHD patients. It is especially relevant in pediatric care, where early detection and intervention can significantly alter disease progression and patient outcomes. This review aims to consolidate current knowledge on the utility of Gal-3 in predicting HF among pediatric patients with CHD, highlighting its potential in changing the direction of diagnosis and treatment in this vulnerable patient population.

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References

  1. Stout KK, Broberg CS, Book WM, et al. Chronic heart failure in congenital heart disease: A scientific statement from the american heart association. Circulation. 2016; 133(8): 770–801.
  2. Kurmani S, Squire I. Acute heart failure: Definition, classification and epidemiology. Curr Heart Fail Rep. 2017; 14(5): 385–392.
  3. Jayaprasad N. Heart failure in children. Heart Views. 2016; 17(3): 92–99.
  4. Hsu D, Pearson G. Heart failure in children. Circ Heart Fail. 2009; 2(1): 63–70.
  5. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–3726.
  6. Benavidez OJ, Gauvreau K, Geva T. Diagnostic errors in congenital echocardiography: importance of study conditions. J Am Soc Echocardiogr. 2014; 27(6): 616–623.
  7. Saraf RP, Suresh Pv, Maheshwari S, et al. Pediatric echocardiograms performed at primary centers: Diagnostic errors and missing links! Ann Pediatr Cardiol. 2015; 8(1): 20–24.
  8. Panagopoulou V, Deftereos S, Kossyvakis C, et al. NTproBNP: An important biomarker in cardiac diseases. Curr Top Med Chem. 2013; 13(2): 82–94.
  9. Argüeso P, Panjwani N. Focus on molecules: Galectin-3. Exp Eye Res. 2011; 92(1): 2–3.
  10. Newlaczyl AU, Yu LG. Galectin-3 — a jack-of-all-trades in cancer. Cancer Lett. 2011; 313(2): 123–128.
  11. Menon RP, Hughes RC. Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur J Biochem. 1999; 264(2): 569–576.
  12. Ruvolo PP. Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta. 2016; 1863(3): 427–437.
  13. de Oliveira FL, Gatto M, Bassi N, et al. Galectin-3 in autoimmunity and autoimmune diseases. Exp Biol Med (Maywood). 2015; 240(8): 1019–1028.
  14. Dumic J, Dabelic S, Flögel M. Galectin-3: An open-ended story. Biochim Biophys Acta. 2006; 1760(4): 616–635.
  15. Issa SF, Christensen AF, Lottenburger T, et al. Within-day variation and influence of physical exercise on circulating Galectin-3 in patients with rheumatoid arthritis and healthy individuals. Scand J Immunol. 2015; 82(1): 70–75.
  16. Dong R, Zhang M, Hu Q, et al. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). Int J Mol Med. 2018; 41(2): 599–614.
  17. Oosterhof T, Tulevski II, Vliegen HW, et al. Effects of volume and/or pressure overload secondary to congenital heart disease (tetralogy of fallot or pulmonary stenosis) on right ventricular function using cardiovascular magnetic resonance and B-type natriuretic peptide levels. Am J Cardiol. 2006; 97(7): 1051–1055.
  18. Kowalik E, Kuśmierczyk-Droszcz B, Klisiewicz A, et al. Galectin-3 plasma levels in adult congenital heart disease and the pressure overloaded right ventricle: reason matters. Biomark Med. 2020; 14(13): 1197–1205.
  19. Slack RJ, Mills R, Mackinnon AC. The therapeutic potential of galectin-3 inhibition in fibrotic disease. Int J Biochem Cell Biol. 2021; 130: 105881.
  20. Sharma UC, Pokharel S, van Brakel TJ, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004; 110(19): 3121–3128.
  21. Guzel S, Serin O, Guzel E, et al. Erratum: Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in myocardial infarction. Korean J Intern Med. 2013; 28(3): 386.
  22. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol. 2008; 172(2): 288–298.
  23. Song X, Qian X, Shen M, et al. Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression. Biochim Biophys Acta. 2015; 1853(2): 513–521.
  24. Hernández-Díaz Y, Tovilla-Zárate CA, Juárez-Rojop I, et al. Association between CRP and tnf-α genes variants and cardiovascular heart disease in a Mexican population: protocol for a case-control study. Int J Environ Res Public Health. 2016; 13(1): 103.
  25. Tsigkou V, Siasos G, Oikonomou E, et al. The prognostic role of galectin-3 and endothelial function in patients with heart failure. Cardiol J. 2023; 30(5): 725–733.
  26. South K, Lane DA. ADAMTS-13 and von Willebrand factor: A dynamic duo. J Thromb Haemost. 2018; 16(1): 6–18.
  27. He J, Li X, Luo H, et al. Galectin-3 mediates the pulmonary arterial hypertension-induced right ventricular remodeling through interacting with NADPH oxidase 4. J Am Soc Hypertens. 2017; 11(5): 275–289.e2.
  28. Ibarrola J, Arrieta V, Sádaba R, et al. Galectin-3 down-regulates antioxidant peroxiredoxin-4 in human cardiac fibroblasts: A new pathway to induce cardiac damage. Clin Sci (Lond). 2018; 132(13): 1471–1485.
  29. Ibarrola J, Sádaba R, Garcia-Peña A, et al. A role for fumarate hydratase in mediating oxidative effects of galectin-3 in human cardiac fibroblasts. Int J Cardiol. 2018; 258: 217–223.
  30. Belch JJ, Bridges AB, Scott N, et al. Oxygen free radicals and congestive heart failure. Br Heart J. 1991; 65(5): 245–248.
  31. Zhong X, Qian X, Chen G, et al. The role of galectin-3 in heart failure and cardiovascular disease. Clin Exp Pharmacol Physiol. 2019; 46(3): 197–203.
  32. Wu CK, Su MY, Lee JK, et al. Galectin-3 level and the severity of cardiac diastolic dysfunction using cellular and animal models and clinical indices. Sci Rep. 2015; 5: 17007.
  33. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372(71): 103–112.
  34. CASP UK. CASP systematic review checklist [Internet]. Oxford: CASP UK; 2018: 4. https://casp-uk.net/wp-content/uploads/2018/01/CASP-Systematic-Review-Checklist_2018.pdf (18.01.2020).
  35. Saleh N, Khattab A, Rizk M, et al. Value of Galectin-3 assay in children with heart failure secondary to congenital heart diseases: A prospective study. BMC Pediatr. 2020; 20(1): 537.
  36. Elhewala AAS, Ibrahem MM, Abdel Hafez ES. Galectin-3 as a biomarker of heart failure in children with congenital heart disease. Egypt J Hosp Med. 2020; 80(3): 1008–1013.
  37. Parker DM, Everett AD, Stabler ME, et al. Novel biomarkers improve prediction of 365-day readmission after pediatric congenital heart surgery. Ann Thorac Surg. 2020; 109(1): 164–170.
  38. Cura C, Argun M, Koçer D. Aldosterone, galectin-3, and NTproBNP levels and their values as biomarkers in infants with ventricular septal defect. Turk Kardiyol Dern Ars. 2022; 50(2): 131–138.
  39. Yang Q, Chen H, Correa A, et al. Racial differences in infant mortality attributable to birth defects in the United States, 1989–2002. Birth Defects Res A Clin Mol Teratol. 2006; 76(10): 706–713.
  40. Mackie AS, Gauvreau K, Newburger JW, et al. Risk factors for readmission after neonatal cardiac surgery. Ann Thorac Surg. 2004; 78(6): 1972–1978; discussion 1978.
  41. Kansagara D, Englander H, Salanitro A, et al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011; 306(15): 1688–1698.
  42. Tregay J, Wray Jo, Bull C, et al. Unexpected deaths and unplanned re-admissions in infants discharged home after cardiac surgery: A systematic review of potential risk factors. Cardiol Young. 2015; 25(5): 839–852.
  43. Brown JR, Stabler ME, Parker DM, et al. Biomarkers improve prediction of 30-day unplanned readmission or mortality after paediatric congenital heart surgery. Cardiol Young. 2019; 29(8): 1051–1056.
  44. Parker DM, Everett AD, Stabler ME, et al. Biomarkers associated with 30-day readmission and mortality after pediatric congenital heart surgery. J Card Surg. 2019; 34(5): 329–336.
  45. Gersony WM. Fontan operation after 3 decades: what we have learned. Circulation. 2008; 117(1): 13–15.
  46. van den Bosch E, Bossers SSM, Kamphuis VP, et al. Associations between blood biomarkers, cardiac function, and adverse outcome in a young fontan cohort. J Am Heart Assoc. 2021; 10(5): e015022.
  47. van der Ven JPG, van den Bosch E, Bogers AdJ, et al. Current outcomes and treatment of tetralogy of Fallot. F1000Res. 2019; 8: 1530.
  48. Luijten LWG, van den Bosch E, Duppen N, et al. Long-term outcomes of transatrial-transpulmonary repair of tetralogy of Fallot. Eur J Cardiothorac Surg. 2015; 47(3): 527–534.
  49. van den Bosch E, van Genuchten WJ, Luijnenburg SE, et al. Associations between blood biomarkers, cardiac function and adverse outcome in a young tetralogy of Fallot cohort. Int J Cardiol. 2022; 361: 31–37.
  50. DiLorenzo MP, DeCost G, Mai AD, et al. Comparison of serum biomarkers of myocardial fibrosis with cardiac magnetic resonance in patients operated for tetralogy of Fallot. Int J Cardiol. 2022; 358: 27–33.
  51. Hoffman JIE, Kaplan S, Liberthson RR, et al. The incidence of congenital heart disease. J Am Coll Cardiol. 2002; 39(12): 1890–1900.
  52. Bocelli A, Favilli S, Pollini I, et al. Prevalence and long-term predictors of left ventricular hypertrophy, late hypertension, and hypertensive response to exercise after successful aortic coarctation repair. Pediatr Cardiol. 2013; 34(3): 620–629.
  53. Klitsie LM, Roest AAW, Kuipers IM, et al. Blood pressure response during exercise in children, adolescents and young adults with a history of aortic coarctation repair. J Hypertens. 2014; 32(7): 1548–1556.
  54. Crepaz R, Cemin R, Romeo C, et al. Factors affecting left ventricular remodelling and mechanics in the long-term follow-up after successful repair of aortic coarctation. Cardiol Young. 2005; 15(2): 160–167.
  55. Frank BS, Urban TT, Lewis K, et al. Circulating biomarkers of left ventricular hypertrophy in pediatric coarctation of the aorta. Congenit Heart Dis. 2019; 14(3): 446–453.
  56. Oeun B, Nakatani D, Hikoso S, et al. Osaka CardioVascular Conference (OCVC) Heart Failure Investigators. Factors associated with elevated N-terminal pro B-type natriuretic peptide concentrations at the convalescent stage and 1-year outcomes in patients with heart failure with preserved ejection fraction. Circ Rep. 2020; 2(8): 400–408.
  57. Jering KS, Claggett BL, Pfeffer MA, et al. Prognostic importance of NT-proBNP (N-terminal pro-b-type natriuretic peptide) following high-risk myocardial infarction in the PARADISE-MI trial. Circ Heart Fail. 2023; 16(5): e010259.
  58. Palazzuoli A, Gallotta M, Quatrini I, et al. Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure. Vasc Health Risk Manag. 2010; 6: 411–418.
  59. Castiglione V, Aimo A, Vergaro G, et al. Biomarkers for the diagnosis and management of heart failure. Heart Fail Rev. 2022; 27(2): 625–643.
  60. Zaborska B, Sikora-Frąc M, Smarż K, et al. The role of galectin-3 in heart failure-the diagnostic, prognostic and therapeutic potential-where do we stand? Int J Mol Sci. 2023; 24(17): 13111.
  61. Takase H, Dohi Y. Kidney function crucially affects B-type natriuretic peptide (BNP), N-terminal proBNP and their relationship. Eur J Clin Invest. 2014; 44(3): 303–308.
  62. Tsutamoto T, Sakai H, Yamamoto T, et al. Renal clearance of N-terminal pro-brain natriuretic peptide is markedly decreased in chronic kidney disease. Circ Rep. 2019; 1(8): 326–332.