Galectin-3: role in the formation of various hemodynamic phenotypes of heart failure and interaction with some neurohumoral factors

Aim. To study the interaction of serum galectin-3 (Gal-3) with fibrogenic factors, cardiac remodeling, as well as parameters of central hemodynamics in various hemodynamic phenotypes of heart failure (HF).

Material and methods. A total of 210 male and female patients with HF were examined (mean age 64,1±1,4 years). HF was established on the basis of patient complaints, medical history, physical examination and laboratory tests using the 2016 ESC Chronic Heart Failure Guidelines. In addition to standard diagnostic tests, enzyme immunoassays were performed: serum Gal-3, aldosterone, matrix metalloproteinase 1 (MMP1), tissue inhibitor of matrix metalloproteinase 1 (TIMP1).

Results. Patients were divided into two groups: group I (n=59) — patients with HF with reduced ejection fraction (LVEF <40%), group II (n=56) — patients with HF with midrange EF (LVEF 41-49%), group III (n=95) — patients with HF with preserved EF (LVEF >50%). Reference values of studied substances were as follows: Gal-3 — 8,6 [3,7; 11,7] ng/ml; aldosterone — 86,8 [47,8; 199,1] pg/ml; MMP1 — 14,5 [8,5; 18,7] ng/ml; TIMP1 — 87,4 [68,6; 115,2] ng/ml. In patients with HF, the levels of Gal-3, aldosterone and TIMP1 increased with the disease functional class (FC). In patients of group I, it significantly increased by 1,7-2,5 (p<0,01), 4,1-5,9 (p<0,05) and 4,1-5,7 (p<0,05); in group II, 1,8-2,8 (p<0,01), 5,6-6,8 (p<0,01) and 6,1-8,3 (p<0,01); in group III, by 2,1-3,1 (p<0,01), 6,1-6,9 (p<0,01) and 6,8-9,3 times (p<0,01), respectively. A positive correlation was established with FC: in groups I and II, Gal-3 had a significant negative relationship with LVEF (p<0,001; p<0,01, respectively); in group III, Gal-3 had a moderate positive relationship with LV posterior wall thickness (p<0,05), interventricular septum thickness (p<0,05), the left ventricle mass index (p<0,01) and LV relative wall thickness (p<0,01).

Conclusion. Levels of Gal-3 and aldosterone increased with HF FC and had a relevant relationship with the activation of some other neurohumoral factors. Gal-3 can be used as an early biomarker of myocardial fibrosis and cardiac remodeling, in predicting and evaluating risk factors, clinical course and outcome of the disease, as well as to assess the effectiveness of treatment in patients with these HF phenotypes.

1. Hrynchyshyn N, Jourdain P, Desnos M, et al. Galectin-3: A New Biomarker for the Diagnosis, Analysis and Prognosis of Acute and Chronic Heart Failure. Arch Cardiovasc Dis. 2013;106(10):541-6. doi:10.1016/j.acvd.2013.06.054.

2. Dubolazova YuV, Drapkina OM. Galectin-3 and NT-proBNP as biomarkers of heart failure decompensation. Russ J Cardiol. 2017;1141:95-101. (In Russ.) doi:10.15829/1560-4071-2017-1-95-101.

3. Kurbonov AK. The value of biological markers in the diagnosis, prediction and evaluation of the effectiveness of treatment of chronic heart failure. Central Asian Journal of Medicine. 2019;1(9):65-73. Available at: https://uzjournals.edu.uz/tma/vol2019/iss1/9.

4. Tseluyko VI, Lozova TA, Sasyuk OS. Galectin-3 as a risk factor for adverse cardiovascular events during long-term observation in patients with right ventricular myocardial infarction on the background of Q myocardial infarction of the posterior wall of the left ventricle. Emergency medicine. 2015;6(69):61-5. (In Russ.) doi: 10.22141/22240586.5.76.2016.76438.

5. Kalan M, Witczak A, Mosiewicz J, et al. Rola galektyny-3 w niewydolnosci serca. Postepy Hig Med Dosw. 2015;69:1107-111.

6. Carrasco-Sanchez FJ, Aramburu-Bodas O, Salamanca-Bautista P, et al. Predictive Value of Serum galectin-3 Levels in Patients With Acute Heart Failure With Preserved Ejection Fraction. Int J Cardiol. 2013:169(3):177-82. doi:10.1016/j.ijcard.2013.08.081

7. Vatutin NT, Shevelyok AN. Influence of comorbidities on blood aldosterone level in chronic heart failure with preserved systolic function of the left ventricle. Cardiovascular Therapy and Prevention. 2017;16(6):92-8. (In Russ.) doi:10.15829/1728-8800-2017-6-92-98.

8. Edelmann F, Holzendorf V, Wachter R, et al. Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial. Eur J Heart Fail. 2015;17:214-23. doi:10.1002/ejhf.203.

9. Amin HZ, Amin LZ, Wijaya IP. Galectin-3: a novel biomarker for the prognosis of heart failure. Clujul Med. 2017;902:129-32. doi:1015386/cjmed-751.

10. Gehlken C, Suthahar N, Meijers WC, et al. Galectin-3 in Heart Failure: An Update of the Last 3 Years. Heart Fail Clin. 2018;14(1):75-92. doi:10.1016/j.hfc.2017.08.009.

11. Kawarazaki W, Fujita T. The Role of Aldosterone in Obesity — Related Hypertension. Am. J. Hypertens. 2016;29(4):415-23. doi:10.1093/ajh/hpw003.

12. Schutten MT, Houben AJ, de Leeuw PW, et al. The Link Between Adipose Tissue Renin — Angiotensin-Aldosterone System Signaling and Obesity — Associated Hypertension. Physiology. 2017;32(3):197-209. doi:10.1152/physiol.00037.2016.

13. Aksenov AI, Polunina OS, Myasoedova EI. Matrix metalloproteinases and their tissue inhibitors in patients with chronic coronary heart disease. Zabaykalsky Medical Bulletin. 2016;4:64-9. (In Russ.)

14. Van Heerebeek L, Paulus WJ. Understanding heart failure with preserved ejection fraction: where are we today? Neth Heart J. 2016;24(4):227-36. doi:101007/s12471-016-0810-1.

15. Moskalenko MI. Involvement of matrix metalloproteinase genes in the formation of arterial hypertension and its complications. Medicine and pharmacy. 2018;4(1):53-69. (In Russ.) doi:1018413/2313-8955-2018-4-1-53-69.

16. Hopps E, Lo Presti R, Caimi G. Metalloproteases in Arterial Hypertension and their Trend after Antihypertensive Treatment. Kidney Blood Press Res. 2017;42:347-57. doi:10.1159/000477785.

17. Medvedeva EA. biomarkers of fibrosis, renal dysfunction and inflammation, their correlations in patients with chronic heart failure of ischemic etiology. Journal of Heart Failure. 2017;18(101):83-6. (In Russ.) doi:10.18087/rhfj.2017.2.2302.

18. McEvoy JW, Chen Y, Halushka MK, et al. Galectin-3 and risk of heart failure and death in blacks and whites. J Am Heart Assoc. 2016;5(5):003079. doi:10.1161/jaha.115.003079.

19. Besler C, Lang D, Urban D, et al. Plasma and Cardiac Galectin — 3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis Circ. Heart Failure. 2017;10(3):003804. doi:10.1161/CIRCHEARTFAILURE.116.003804.

20. Li P, Liu S, Lu M, et al. The galactopoietic derivative galectin-3 induces cellular and systemic insulin resistance. Cell. 2016;167:973-84. doi:10.1016/j.cell.2016.10.025.

21. Suthahar N, Meijers WC, Sillje HHW, et al. Activation and inhibition of galectin-3 in heart failure and cardiovascular disease: update. Theranostics. 2018;8(3):593-609. doi:10.7150/thno.22196.