Abstract

Hart failure (HF) accounts for numerous serious problems: medical, social and financial. HF affects 2-3% adult population and its frequency increases with age. Despite advances in laboratory diagnostics of HR the use of biochemical markers remains limited. Currently, only natriuretic peptides, especially type B natriuretic peptides (BNP) and N-terminal fragment of pro-BNP (NT-proBNP) have been fully approved biomarkers employed in diagnosing HF. The concentration of those peptides fluctuates and largely depends on age, gender, renal function, day/night rhythm and volemia which reflects hemodynamic state rather than hart abnormal structure. As the application of natriuretic peptides is limited in certain groups of patients, it is necessary to search for other more stable biomarkers. Recent investigations have suggested galectin-3 (gal-3) to be a new promising cardiological marker. Gal-3 belongs to a family of lectins that demonstrate binding specificity for β-galactoside which are produced by activated macrophages. Its operative path involves stimulation of cardiac fibroblasts and collagen production which can result in pathological remodeling of the myocardium structure. Numerous research found substantially increased gal-3 level in patients with chronic HF disregarding the etiology of disease. Moreover, some clinical studies have proved that increased gal-3 concentration is a factor of poor prognosis and predicative of death due to any reason in patients with HF. Contrary to natriuretic peptides, gal-3 is hemodynamically stable which is an additional asset of gal-3 as a marker of myocardial fibrosis.The article presents current state of research into gal-3 involvement in HF pathogenesis and possible use of gal-3 as a diagnostic marker of HF.

References

• 1. Argüeso P., Panjwani N.: Focus on Molecules: Galectin-3. ExperimentalEye Res., 2011; 9: 2-3
  Google Scholar
• 2. Cowie M. R.,Mosterd A.,Wood D. A., Deckers J. W., Poole- WilsonP. A.,Sutton G. C., Grobbee D. E..: The epidemiology of heartfailure. Eur. Heart J., 1997; 18: 208-225
  Google Scholar
• 3. de Boer R. A., van Veldhuisen D.J., Gansvoort R. T., Muller KoboldA.C., van Gilst W.H., Hillege H.L., Bakker S.J.L., van der HarstP.: The fibrosis marker galectin-3 and outcome in the generalpopulation. J. Int. Med. 2012; 272: 55-64
  Google Scholar
• 4. de Boer R. A.,Yu L., van Veldhuisen D.J.: Galectin-3 in Cardiac Remodeling and Heart Failure. Curr. Heart Fail. Rep., 2010; 7: 1-8
  Google Scholar
• 5. de Boer R.A., Voors A. A., Muntendam P., van Gilst W.H., vanVeldhuisen D.J .: Galectin-3: a novel mediator of heart failure developmentand progression. Eur. J. Heart Fail., 2009; 11: 811-817
  Google Scholar
• 6. deFilippi C. R., Felker G. M.: Galectin-3 in Heart Failure – LinkingFibrosis, Remodelling and Progression European Cardiology,2010; 6 (2): 33–36
  Google Scholar
• 7. Drożdż J.: Nowości w diagnostyce i leczeniu niewydolnościserca 2009. Kardiologia na co Dzień, 2009; 4 (2): 63-66
  Google Scholar
• 8. Dumic J., Dabelic S., Flögel M.: Galectin-3: An open-ended story.Biochim. Biophys. Acta, 2006; 1760: 616–635
  Google Scholar
• 9. Fiuzat M, Schulte PJ, Felker M, Ahmad T, Neely M, Adams KF,et al. Relationship between galectin-3 levels and mineralocorticoidreceptor antagonist use in heart failure: analysis from HF–ACTION. J Card Fail. 2014; 20(1):38-44
  Google Scholar
• 10. Henderson N. C., Mackinnon A. C, Farnworth S. L.,Kipari T,Haslett C.,Iredale J. P.,Liu F., Hughes J., Sethi T.: Galectin-3 Expressionand Secretion Links Macrophages to the Promotion of RenalFibrosis. Am. J. Pathol., 2008, 172, 2, 288-298
  Google Scholar
• 11. Henderson N.C., Mackinnon A. C., Farnworth S. L., PoirierF., Russo F. P., Iredale J. P., Haslett C., Simpson K. J., Sethi T.: Galectin-3regulates myofibroblast activation and hepatic fibrosis.PNAS, 2006; 103: 5060-5065
  Google Scholar
• 12. Ho J.E., Liu C.,Lyass A., Courchessne P., Pencina M. J., VasanR.S., Larson M. G., Levy D.: Galectin-3, a Marker of Cardiac Fibrosis,Predicts Incident Heart Failure in the Community. J. Am. Coll.Cardiol., 2012; 60: 1249-56
  Google Scholar
• 13. Hughes R.C.: Mac-2: a versatile galactose-binding protein ofmammalian issues. Glycobiology, 1994; 4: 5-12
  Google Scholar
• 14. Hughes R.C.: Secretion of the galectin family of mammaliancarbohydrate-binding proteins. Biochim. Biophys. Acta., 1999;1473: 172-185
  Google Scholar
• 15. Klecha A., Bacior B., Styczkiewicz K., Kawecka-JaszczK.: Treningfizyczny u chorych w podeszłym wieku z przewlekłą niewydolnościąserca. Medycyna Wieku Podeszłego, 2011; 1: 77–81
  Google Scholar
• 16. Koukoui F., Desmoulin F., Galinier M., Barutaut M., Caub C.,Evaristi M. F., Murat G., De Boer R., Berry M., Smih F., Rouet P.:The Prognostic Value of Plasma Galectin-3 in Chronic Heart FailurePatients Is Maintained when Treated with MineralocorticoidReceptor Antagonists. PLoS One, 2015, 18 10 (3): e0119160. doi:10.1371/journal.pone.0119160. eCollection 2015.
  Google Scholar
• 17. Kramer F.: Galectin-3: Clinical utility and prognostic Valuein patients with heart failure. Res. Reports Clin. Cardiol., 2013;4: 13-22
  Google Scholar
• 18. Krasek D., Kubica A., Sinkiewicz W. Błażejewski J., Bujak R.:Epidemia niewydolności serca- problem zdrowotny i społecznystarzejących się społeczeństw Polski i Europy. Fol. Card. Exc.,2008; 3: 242-248
  Google Scholar
• 19. Krześlak A., Lipińska A.A.: Galectin-3 as a multifunctionalprotein. Cell Moll. Biol. Let, 2004; 9: 305-328
  Google Scholar
• 20. Lin Y.H., Lin L.Y., Wu Y.W., Chien K. L., Lee C. M., Hsu R. B.,Chao C. L., Wang S.S., Hsein Y. C., Liao L.C., Ho Y. L.,Chen M.F.:The relationship between serum galectin -3 and serum markersof cardiac extracellular matrix turnover in heart failure patients.Clin. Chim. Acta., 2009; 409: 96 -99
  Google Scholar
• 21. Lipka D., Boratyński J.: Metaloproteinazy MMP. Strukturai funkcja. Postepy Hig. Med. Dosw., 2008; 62: 328-336
  Google Scholar
• 22. Liu Y., Ambrosio M. D., Liao T., Peng H., Rhaleb N., Sharma U.,Andre A., Gabius H., Carretero O. A.: N-acetyl-seryl-aspartyl-lysyl–proline prevents cardiac remodeling and dysfunction inducedby galectin-3, a mammalian adhesion/growth-regulatory lectin. Am. J. Physiol. Heart Circ. Physiol., 2009; 296: 404-412
  Google Scholar
• 23. Lok D. J, Van Der Meer P., de la Porte P. W.,Lipsic E., VanWijngaarden J., Hillege H. L., van Veldhuisen D. J.: Prognosticvalue of galectin‑3,a novel marker of fibrosis, in patients withchronic heart failure: data from the deal‑hf study. Clin. Res. Cardiol.,2010;99:323‑328
  Google Scholar
• 24. Marchel M., Filipiak K. J.: Współczesna diagnostyka biochemicznaniewydolności serca- w poszukiwaniu nowych markerów.Pol. Przegl. Kardiol., 2003; 4: 397-407
  Google Scholar
• 25. Mc Murray J.J.V., Adamopoulos S., Anker S.D., Auricchio A.,Bohm M., Dickstein K., Falk V., Filippatos G., Fonseca C., GomezSanchezM.A., Jaarsma T., Kober L., Parkhomenko A., MaggioniA.P., Lip G.Y.H. i wsp.: ESC Guidelines for the diagnosis and treatmentof acute and chronic heart failure 2012 The Task Force forthe Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaborationwith the Heart Failure Association (HFA) of the ESC. Eur.Heart J., 2012; 33: 1787-1847
  Google Scholar
• 26. Milting H., Ellinghaus P., Seewald M., Cakar H., Bohms B.,Kassner A., Korfer R., Klein M., Krahn T., Kruska L., El BanayosyA., Kramer F.:Plasma biomarkers of myocardial fibrosis and remodelingin terminal heart failure patients supported by mechanicalcirculatory support devices. J. Heart Lung Transplant.,2008;27:589‑596
  Google Scholar
• 27. Morrow D. A., M.D., M.P.H., O’Donoghue M.L.: Galectin-3 inCardiovascular Disease: A possible window into early MyocardialFibrosis J. Am. Coll. Cardiol., 2012; 60: 1257-8
  Google Scholar
• 28. Pinnelli V., Sirsiker M., Silvia W. D.: Galectin-3: A Novel Biomarker.International Journal of Chemical And PharmaceuticalResearch, 2013; 2: 81-94
  Google Scholar
• 29. Pokrywka M., Lityńska A.: Budowa I funkcje biologiczne galektyny-3.Część I. Postępy Biol. Komórki, 2010; 37:677-684
  Google Scholar
• 30. Rojek A., Kosmala W.: Udział galektyn w patofizjologii schorzeńukładu sercowo- naczyniowego. Pol. Przegl. Kardiol., 213;15: 55- 59
  Google Scholar
• 31. Shah R.V., Chen-Tournoux A.A., Picard M.H., van KimmenadeR. R., Januzzi J. L.: Galectin-3,cardiac structure and function,and long-term mortality in patients with acutely decompensatedheart failure. Eur. J. Heart Fail., 2010;12:826‑832
  Google Scholar
• 32. Sharma U. C., Pokharel S., van Brakel T. J., van Berlo J. H.,Cleutjens J. P., Schroen B., Andre S., Crijns H. J., Gabius H. J., MaessenJ., Pinto Y. M.: Galectin-3 Marks Activated Macrophages inFailure-Prone Hypertrophied Hearts and Contributes to CardiacDysfunction. Circulation, 2004; 110: 3121-3128
  Google Scholar
• 33. Sharma U., Rhaleb N., Pokharel S., Harding P., Rasoul., PengH., Carretero O. A.: Novel anti-inflammatory mechanisms of N–Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organdamage. Am. J. Physiol. Heart Circ. Physiol., 2008; 294: 1226-1232
  Google Scholar
• 34. Szadkowska I., Wlazeł R., Paradowski M., Pawlicki L.: Galektyna-3.Aktualności bioMerieux, 2012; 63: 3-5
  Google Scholar
• 35. Van Kimmenade R. R., Januzzi J.L., Ellinor P. T., Sharma U. C.,Bakker J. A., Low A. F., Martinez A., Crijns H. J., MacRae C. A.,MenheereP. P., Pinto Y.M.: Utility of Amino-Terminal Pro-BrainNatriureticPeptide, Galectin-3, and Apelinfor the Evaluation of PatientsWith Acute Heart Failure. J. Am. Coll. Cardiol., 2006; 48: 1217- 122
  Google Scholar
• 36. Yu L., de Boer R. A.,Ph. D., F. E. S. C.: Role of Galectin-3 pathwaysin the pathogenesis of cardiac remodeling and heart failure.W: Cardiac Remodeling Molecular Mechanisms, t.5, red.: JugduttB.J, Dhalla N. S. Springer, New York 2013, 97-111
  Google Scholar

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