An overview about galectin-3 and its relationship with cardiovascular diseases

Abstract

Inflammation is one of the cornerstones of atherosclerosis. Galectin-3 (Gal-3) acts on the stages of the inflammatory process. Gal-3 is a candidate for being a valuable marker for heart failure (HF) and coronary artery disease (CAD). Further studies are needed for the diagnosis and follow-up of CAD. In the literature, the relationship between Gal-3 and CAD has not been researched sufficiently. We aimed to write a review by referring to recent studies about Gal-3 in the etiopathogenesis of CAD, its prognostic significance, and its contribution to the treatment regimen.

Keywords

• Atherosclerosis
• Galectin-3
• İnflammation
• Heart failure
• Coronary artery disease

References

1. 1. Askin L, Tanrıverdi O. An Overview of Clinical Studies on Endocan and Cardiovascular Disease. Erciyes Med J. 2021;43(3):233-6. doi: 10.14744/etd.2020.09699.
2. 2. Blanda V, Bracale UM, Di Taranto MD, Fortunato G. Galectin-3 in Cardiovascular Diseases. Int J Mol Sci. 2020;21(23):9232. doi: 10.3390/ijms21239232.
3. 3. Maiolino G, Rossitto G, Pedon L, Cesari M, Frigo AC, Azzolini M, et al. Galectin-3 predicts long-term cardiovascular death in high-risk patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2015;35(3):725-32. doi: 10.1161/ATVBAHA.114.304964.
4. 4. Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230(1):160-71. doi: 10.1111/j.1600-065X.2009.00794.x.
5. 5. Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110(19):3121-8. doi: 10.1161/01.CIR.0000147181.65298.4D.
6. 6. Kusaka H, Yamamoto E, Hirata Y, Fujisue K, Tokitsu T, Sugamura K, et al. Clinical significance of plasma galectin-3 in patients with coronary artery disease. Int J Cardiol. 2015;201:532-4. doi: 10.1016/j.ijcard.2015.08.099.
7. 7. Chen A, Hou W, Zhang Y, Chen Y, He B. Prognostic value of serum galectin-3 in patients with heart failure: a meta-analysis. Int J Cardiol. 2015;182:168-70. doi: 10.1016/j.ijcard.2014.12.137.
8. 8. Reifenberg K, Lehr HA, Torzewski M, Steige G, Wiese E, Küpper I, et al. Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice. Am J Pathol. 2007;171(2):463-72. doi: 10.2353/ajpath.2007.060906.

9. 9. Yu L, Ruifrok WP, Meissner M, Bos EM, van Goor H, Sanjabi B, et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6(1):107-17. doi: 10.1161/CIRCHEARTFAILURE.112.971168.
10. 10. Lepojärvi ES, Piira OP, Pääkkö E, Lammentausta E, Risteli J, Miettinen JA, et al. Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties. Front Physiol. 2015;6:200. doi: 10.3389/fphys.2015.00200.
11. 11. McCullough PA. Practical experience using galectin-3 in heart failure. Clin Chem Lab Med. 2014;52(10):1425-31. doi: 10.1515/cclm-2014-0278.
12. 12. Meijers WC, Januzzi JL, deFilippi C, Adourian AS, Shah SJ, van Veldhuisen DJ, et al. Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: a pooled analysis of 3 clinical trials. Am Heart J. 2014;167(6):853-60.e4. doi: 10.1016/j.ahj.2014.02.011.
13. 13. Hashmi S, Al-Salam S. Galectin-3 is expressed in the myocardium very early post-myocardial infarction. Cardiovasc Pathol. 2015;24(4):213-23. doi: 10.1016/j.carpath.2014.12.001.
14. 14. Coromilas E, Que-Xu EC, Moore D, Kato TS, Wu C, Ji R, et al. Dynamics and prognostic role of galectin-3 in patients with advanced heart failure, during left ventricular assist device support and following heart transplantation. BMC Cardiovasc Disord. 2016;16:138. doi: 10.1186/s12872-016-0298-z.
15. 15. Rieth AJ, Jung C, Gall H, Rolf A, Mitrovic V, Hamm CW, et al. Association of galectin-3 with changes in left ventricular function in recent-onset dilated cardiomyopathy. Biomarkers. 2019;24(7):652-658. doi: 10.1080/1354750X.2019.1642959.
16. 16. Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol. 2012;60(14):1249-56. doi: 10.1016/j.jacc.2012.04.053.
17. 17. Liu YH, D'Ambrosio M, Liao TD, Peng H, Rhaleb NE, Sharma U, 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(2):H404-12. doi: 10.1152/ajpheart.00747.2008.
18. 18. Calvier L, Miana M, Reboul P, Cachofeiro V, Martinez-Martinez E, de Boer RA, et al. Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol. 2013;33(1):67-75. doi: 10.1161/ATVBAHA.112.300569.
19. 19. Lax A, Sanchez-Mas J, Asensio-Lopez MC, Fernandez-Del Palacio MJ, Caballero L, Garrido IP, et al. Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction. JACC Heart Fail. 2015;3(1):50-58. doi: 10.1016/j.jchf.2014.07.015.
20. 20. Yakar Tülüce S, Tülüce K, Çil Z, Emren SV, Akyıldız Zİ, Ergene O. Galectin-3 levels in patients with hypertrophic cardiomyopathy and its relationship with left ventricular mass index and function. Anatol J Cardiol. 2016;16(5):344-8. doi: 10.5152/AnatolJCardiol.2015.6191.
21. 21. de Boer RA, Edelmann F, Cohen-Solal A, Mamas MA, Maisel A, Pieske B. Galectin-3 in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013;15(10):1095-101. doi: 10.1093/eurjhf/hft077.
22. 22. Pugliese G, Iacobini C, Ricci C, Blasetti Fantauzzi C, Menini S. Galectin-3 in diabetic patients. Clin Chem Lab Med. 2014;52(10):1413-23. doi: 10.1515/cclm-2014-0187.
23. 23. Seferovic JP, Lalic NM, Floridi F, Tesic M, Seferovic PM, Giga V, et al. Structural myocardial alterations in diabetes and hypertension: the role of galectin-3. Clin Chem Lab Med. 2014;52(10):1499-505. doi: 10.1515/cclm-2014-0265.
24. 24. Tan KCB, Cheung CL, Lee ACH, Lam JKY, Wong Y, Shiu SWM. Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus. Diabetologia. 2018;61(5):1212-1219. doi: 10.1007/s00125-018-4552-z.
25. 25. Weigert J, Neumeier M, Wanninger J, Bauer S, Farkas S, Scherer MN, et al. Serum galectin-3 is elevated in obesity and negatively correlates with glycosylated hemoglobin in type 2 diabetes. J Clin Endocrinol Metab. 2010;95(3):1404-11. doi: 10.1210/jc.2009-1619
26. 26. Li P, Liu S, Lu M, Bandyopadhyay G, Oh D, Imamura T, et al. Hematopoietic-Derived Galectin-3 Causes Cellular and Systemic Insulin Resistance. Cell. 2016;167(4):973-984.e12. doi: 10.1016/j.cell.2016.10.025.
27. 27. Johnson AMF, Hou S, Li P. Inflammation and insulin resistance: New targets encourage new thinking: Galectin-3 and LTB4 are pro-inflammatory molecules that can be targeted to restore insulin sensitivity. Bioessays. 2017;39(9):10.1002/bies.201700036. doi: 10.1002/bies.201700036.
28. 28. Pang J, Rhodes DH, Pini M, Akasheh RT, Castellanos KJ, Cabay RJ, et al. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice. PLoS One. 2013;8(2):e57915. doi: 10.1371/journal.pone.0057915.
29. 29. Iacobini C, Menini S, Ricci C, Scipioni A, Sansoni V, Cordone S, et al. Accelerated lipid-induced atherogenesis in galectin-3-deficient mice: role of lipoxidation via receptor-mediated mechanisms. Arterioscler Thromb Vasc Biol. 2009;29(6):831-6. doi: 10.1161/ATVBAHA.109.186791.
30. 30. Tsai TH, Sung PH, Chang LT, Sun CK, Yeh KH, Chung SY, et al. Value and level of galectin-3 in acute myocardial infarction patients undergoing primary percutaneous coronary intervention. J Atheroscler Thromb. 2012;19(12):1073-82. doi: 10.5551/jat.12856.
31. 31. Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, et al. The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Am Heart J. 2012;164(6):878-83. doi: 10.1016/j.ahj.2012.08.021.
32. 32. Falcone C, Lucibello S, Mazzucchelli I, Bozzini S, D'Angelo A, Schirinzi S, et al. Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome. Int J Immunopathol Pharmacol. 2011;24(4):905-13. doi: 10.1177/039463201102400409.
33. 33. Menini S, Iacobini C, Ricci C, Blasetti Fantauzzi C, Salvi L, Pesce CM, et al. The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis. Cardiovasc Res. 2013;100(3):472-80. doi: 10.1093/cvr/cvt206.
34. 34. Mayr A, Klug G, Mair J, Streil K, Harrasser B, Feistritzer HJ, et al. Galectin-3: relation to infarct scar and left ventricular function after myocardial infarction. Int J Cardiol. 2013;163(3):335-337. doi: 10.1016/j.ijcard.2012.06.087.
35. 35. Gao Z, Liu Z, Wang R, Zheng Y, Li H, Yang L. Galectin-3 Is a Potential Mediator for Atherosclerosis. J Immunol Res. 2020;2020:5284728. doi: 10.1155/2020/5284728.
36. 36. Winter MP, Wiesbauer F, Alimohammadi A, Blessberger H, Pavo N, Schillinger M, et al. Soluble galectin-3 is associated with premature myocardial infarction. Eur J Clin Invest. 2016;46(5):386-91. doi: 10.1111/eci.12605.
37. 37. Aksan G, Gedikli Ö, Keskin K, Nar G, İnci S, Yıldız SS, et al. Is galectin-3 a biomarker, a player-or both-in the presence of coronary atherosclerosis? J Investig Med. 2016;64(3):764-70. doi: 10.1136/jim-2015-000041.
38. 38. Gleissner CA, Erbel C, Linden F, Domschke G, Akhavanpoor M, Doesch AO, et al. Galectin-3 binding protein plasma levels are associated with long-term mortality in coronary artery disease independent of plaque morphology. Atherosclerosis. 2016;251:94-100. doi: 10.1016/j.atherosclerosis.2016.06.002.
39. 39. Ho JE, Yin X, Levy D, Vasan RS, Magnani JW, Ellinor PT, et al. Galectin 3 and incident atrial fibrillation in the community. Am Heart J. 2014;167(5):729-34.e1. doi: 10.1016/j.ahj.2014.02.009.
40. 40. Sonmez O, Ertem FU, Vatankulu MA, Erdogan E, Tasal A, Kucukbuzcu S, et al. Novel fibro-inflammation markers in assessing left atrial remodeling in non-valvular atrial fibrillation. Med Sci Monit. 2014;20:463-70. doi: 10.12659/MSM.890635.
41. 41. Gurses KM, Yalcin MU, Kocyigit D, Canpinar H, Evranos B, Yorgun H, et al. Effects of persistent atrial fibrillation on serum galectin-3 levels. Am J Cardiol. 2015;115(5):647-51. doi: 10.1016/j.amjcard.2014.12.021.
42. 42. Kocyigit D, Gurses KM, Yalcin MU, Canpinar H, Canpolat U, Evranos B, et al. Serum galectin-3 level as a marker of thrombogenicity in atrial fibrillation. J Clin Lab Anal. 2017;31(6):22120. doi: 10.1002/jcla.22120.
43. 43. Clementy N, Benhenda N, Piver E, Pierre B, Bernard A, Fauchier L, et al. Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation. Sci Rep. 2016;6:34357. doi: 10.1038/srep34357.
44. 44. Clementy N, Piver E, Bisson A, Andre C, Bernard A, Pierre B, et al. Galectin-3 in Atrial Fibrillation: Mechanisms and Therapeutic Implications. Int J Mol Sci. 2018;19(4):976. doi: 10.3390/ijms19040976.
45. 45. Numano F, Shimizu C, Jimenez-Fernandez S, Vejar M, Oharaseki T, Takahashi K, et al. Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms. Int J Cardiol. 2015;201:429-37. doi: 10.1016/j.ijcard.2015.07.063.