Current Heart Failure Reports

, Volume 7, Issue 1, pp 1–8 | Cite as

Galectin-3 in Cardiac Remodeling and Heart Failure

  • Rudolf A. de Boer
  • Lili Yu
  • Dirk J. van Veldhuisen


Galectin-3 is a member of the galectin family, which consists of animal lectins that bind β-galactosides. Recently, a role for galectin-3 in the pathophysiology of heart failure has been suggested. It was observed that galectin-3 is specifically upregulated in decompensated heart failure compared with compensated heart failure in animal models of heart failure. This has been associated with activation of fibroblasts and macrophages, which are a hallmark of cardiac remodeling. Therefore, galectin-3 may be a culprit biomarker in heart failure. Initial clinical observations indicate that galectin-3 may be a useful biomarker for decompensated heart failure, with incremental value over well-used “pressure-dependent” biomarkers, such as B-type natriuretic peptide. Future studies should focus on galectin-3 biology to better address the usefulness of galectin-3 as a biomarker and probe the usefulness of anti-galectin-3 therapy in treating heart failure.


Galectin 3 Heart failure Prognosis Fibrosis Macrophages Biomarkers Renin-angiotensin system 



This work was supported by the Netherlands Heart Foundation (grant 2007T046 to Dr. de Boer) and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VENI, grant 016.106.117, also to Dr. de Boer).


No potential conflicts of interest relevant to this article were reported.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


Papers of particular interest, published recently have been highlighted as • Of importance •• Of major importance

  1. 1.
    Barondes SH, Cooper DNW, Gitt MA, Leffler H: Galectins: structure and function of a large family of animal lectins. J Biol Chem 1994, 269:20807–20810.PubMedGoogle Scholar
  2. 2.
    Cooper DN: Galectinomics: finding themes in complexity. Biochim Biophys Acta 2002, 1572:209–231.PubMedCrossRefGoogle Scholar
  3. 3.
    Wang JL, Laing JG, Anderson RL: Lectins in the cell nucleus. Glycobiology 1991, 3:243–252.CrossRefGoogle Scholar
  4. 4.
    •• Yang RY, Rabinovich GA, Liu FT: Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 2008, 13:e17–e39. This excellent review article provides insight regarding galectin biology.CrossRefGoogle Scholar
  5. 5.
    Elola MT, Wolfenstein-Todel C, Troncoso MF, et al.: Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci 2007, 64:1679–1700.PubMedCrossRefGoogle Scholar
  6. 6.
    Liu FT, Patterson RJ, Wang JL: Intracellular functions of galectins. Biochim Biophys Acta 2002, 1572:263–273.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang JL, Laing JG, Anderson RL: Lectins in the cell nucleus. Glycobiology 1991, 3:243–252.CrossRefGoogle Scholar
  8. 8.
    Hughes RC: Mac-2: a versatile galactose-binding protein of mammalian tissues. Glycobiology 1994, 4:5–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Birdsall B, Feeney J, Burdett IDJ, et al.: NMR solution studies of hamster galectin-3 and electron microscopic visualization of surface-adsorbed complexes: evidence for interactions between the N-and C-terminal domains. Biochemistry 2001, 40:4859–4866.PubMedCrossRefGoogle Scholar
  10. 10.
    Krześlak A, Lipińska A: Galectin-3 as a multifunctional protein. Cell Mol Biol Lett 2004, 9:305–328.PubMedGoogle Scholar
  11. 11.
    Rosenberg I, Cherayil BJ, Isselbacher KJ, Pillai S: Mac-2-binding glycoproteins. Putative ligands for a cytosolic β-galactoside lectin. J Biol Chem 1991, 266:18731–18736.Google Scholar
  12. 12.
    Sato S, Hughes RC: Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. J Biol Chem 1992, 267:6983–6990.PubMedGoogle Scholar
  13. 13.
    Ochieng J, Furtak V, Lukyanov P: Extracellular functions of galectin-3. Glycoconj J 2004, 19:527–535.PubMedCrossRefGoogle Scholar
  14. 14.
    Nakahara S, Oka N, Wang Y, et al.: Characterization of the nuclear import pathways of galectin-3. Cancer Res 2006, 66:9995–10006.PubMedCrossRefGoogle Scholar
  15. 15.
    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, 264:569–576.PubMedCrossRefGoogle Scholar
  16. 16.
    Mehul B, Hughes RC: Plasma membrane targeting, vesicular budding and release of galectin 3 from the cytoplasm of mammalian cells during secretion. J Cell Sci 1997, 110:1169–1178.PubMedGoogle Scholar
  17. 17.
    Hughes RC: The galectin family of mammalian carbohydrate-binding molecules. Biochem Soc Transact 1997, 25:1194–1198.Google Scholar
  18. 18.
    Hughes RC: Secretion of the galectin family of mammalian carbohydrate-binding family proteins. Biochem Biophys Acta 1999, 1473:172–185.PubMedCrossRefGoogle Scholar
  19. 19.
    Kim H, Lee J, Hyun JW, et al.: Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int 2007, 31:655–662.PubMedCrossRefGoogle Scholar
  20. 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, 110:3121–3128.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee MA, Böhm M, Paul M, et al.: Physiological characterization of the hypertensive transgenic rat TGR(mREN2)27. Am J Physiol 1996, 270:E919–E929.PubMedGoogle Scholar
  22. 22.
    de Boer RA, Pokharel S, Flesch M, et al.: Extracellular signal regulated kinase and SMAD signaling both mediate the angiotensin II driven progression towards overt heart failure in homozygous TGR(mRen2)27. J Mol Med 2004, 82:678–687.PubMedCrossRefGoogle Scholar
  23. 23.
    Schroen B, Heymans S, Sharma U, et al.: Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res 2004, 95:515–522.PubMedCrossRefGoogle Scholar
  24. 24.
    Thandavarayan RA, Watanabe K, Ma M, et al.: 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy. Biochem Pharmacol 2008, 75:1797–1806.PubMedCrossRefGoogle Scholar
  25. 25.
    Sharma U, Rhaleb NE, Pokharel S, et al.: Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage. Am J Physiol 2008, 294:H1226–H1232.Google Scholar
  26. 26.
    • Liu YH, D’Ambrosio M, Liao TD, et al.: N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. Am J Physiol Heart Circ Physiol 2009, 296:H404–H412. This article evaluates anti-galectin-3 therapy and demonstrates how it may reverse adverse cardiac remodeling, providing support for the hypothesis that anti-galectin therapy may be feasible.PubMedCrossRefGoogle Scholar
  27. 27.
    Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000, 275:2247–2250.PubMedCrossRefGoogle Scholar
  28. 28.
    Brown RD, Ambler SK, Mitchell MD, Long CS: The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol 2005, 45:657–687.PubMedCrossRefGoogle Scholar
  29. 29.
    de Cavanagh EM, Ferder M, Inserra F, Ferder L: Angiotensin II, mitochondria, cytoskeletal, and extracellular matrix connections: an integrating viewpoint. Am J Physiol Heart Circ Physiol 2009, 296:H550–H558.PubMedCrossRefGoogle Scholar
  30. 30.
    Hsu DK, Dowling CA, Jeng KC, et al.: Galectin-3 expression is induced in cirrhotic liver and hepatocellular carcinoma. Int J Cancer 1999, 81:519–526.PubMedCrossRefGoogle Scholar
  31. 31.
    Henderson NC, Mackinnon AC, Farnworth SL, et al.: Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci USA 2006, 103:5060–5065.PubMedCrossRefGoogle Scholar
  32. 32.
    Nishi Y, Sano H, Kawashima T, et al.: Role of galectin-3 in human pulmonary fibrosis. Allergol Int 2007, 56:57–65.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang L, Friess H, Zhu Z, et al.: Galectin-1 and galectin-3 in chronic pancreatitis. Lab Invest 2000, 80:1223–1241.CrossRefGoogle Scholar
  34. 34.
    Sasaki S, Bao Q, Hughes RC: Galectin-3 modulates rat mesangial cell proliferation and matrix synthesis during experimental glomerulonephritis induced by anti-Thy1.1 antibodies. J Pathol 1999, 187:481–489.PubMedCrossRefGoogle Scholar
  35. 35.
    • 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, 172:288–298. This experimental study underscores the pivotal role of galectin-3 in the fibrosis process. Employing galectin-3 deficient mice, the authors show that galectin-3 regulates renal fibrosis.PubMedCrossRefGoogle Scholar
  36. 36.
    Eis V, Luckow B, Vielhauer V, et al.: Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. J Am Soc Nephrol 2004, 15:337–347.PubMedCrossRefGoogle Scholar
  37. 37.
    Vlassara H, Li YM, Imani F, et al.: Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex. Mol Med 1995, 1:634–646.PubMedGoogle Scholar
  38. 38.
    Hartog JW, Voors AA, Bakker SJ, et al.: Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications. Eur J Heart Fail 2007, 9:1146–1155.PubMedCrossRefGoogle Scholar
  39. 39.
    Iacobini C, Oddi G, Menini S, et al.: Development of age-dependent glomerular lesions in galectin-3/AGE-receptor-3 knockout mice. Am J Physiol 2005, 289:F611–F621.CrossRefGoogle Scholar
  40. 40.
    Iacobini C, Menini S, Oddi G, et al.: Galectin-3/AGE-receptor 3 knockout mice show accelerated AGE-induced glomerular injury: evidence for a protective role of galectin-3 as an AGE receptor. FASEB J 2004, 18:1773–1775.PubMedGoogle Scholar
  41. 41.
    Frangogiannis NG: The immune system and cardiac repair. Pharmacol Res 2008, 58:88–111.PubMedCrossRefGoogle Scholar
  42. 42.
    Reifenberg K, Lehr HA, Torzewski M, et al.: Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice. Am J Pathol 2007, 171:463–472.PubMedCrossRefGoogle Scholar
  43. 43.
    van Kimmenade RR, Januzzi JL Jr, Ellinor PT, et al.: Utility of aminoterminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure. J Am Coll Cardiol 2006, 48:1217–1224.PubMedCrossRefGoogle Scholar
  44. 44.
    Milting H, Ellinghaus P, Seewald M, et al.: Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices. J Heart Lung Transplant 2008, 27:589–596.PubMedCrossRefGoogle Scholar
  45. 45.
    Lin YH, Lin LY, Wu YW, et al.: The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients. Clin Chim Acta 2009, 409:96–99.PubMedCrossRefGoogle Scholar
  46. 46.
    • de Boer RA, Voors AA, Muntendam P, et al.: Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail 2009, 11:811–817. This article provides a complete overview of the potential role of galectin-3 in the pathophysiology of heart failure.PubMedCrossRefGoogle Scholar
  47. 47.
    Dickstein K, Cohen-Solal A, Filippatos G, et al.: ESC guidelines for the diagnosis treatment of acute, chronic heart failure 2008. The task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008, 10:933–989.PubMedCrossRefGoogle Scholar

Copyright information

© The Author(s) 2010

Authors and Affiliations

  • Rudolf A. de Boer
    • 1
  • Lili Yu
    • 1
  • Dirk J. van Veldhuisen
    • 1
  1. 1.Department of Cardiology, Division of Experimental CardiologyUniversity Medical Center GroningenGroningenThe Netherlands

Personalised recommendations