Galectin-3 as a marker and mediator of endogenous inflammation and nitrosylation oxidative stress in patients with chronic heart failure

Aim. To investigate the association between plasma levels of galectin-3 and parameters of endogenous inflammation and nitrosylation oxidative stress (NOS) in patients with decompensated chronic heart failure (CHF).

Material and methods. In total, 197 CHF patients with myocardial infarction in medical history were divided into 3 groups: Group 1 (n=56) with Functional Class (FC) II CHF IIA; Group 2 (n=72) with FC III CHF IIA; and Group 3 (n=69) with FC IV CHF IIB. The control group (CG) included 39 healthy individuals. Plasma levels of galectin-3, 3-nitrotyrosine, low-density lipoprotein (LDL) oxidation, EC-SOD activity, interleukin-6, and high-sensitivity C-reactive protein (hsCRP) were measured.

Results. In Groups 1, 2, and 3, plasma levels of galectin-3 were significantly higher than in CG: by 39% (p<0,05), 164% (p<0,001), and 428% (p<0,001), respectively.

The activity of NOS increased in parallel with CHF FC: by 24% (p<0,05) in Group 1, by 81% (p<0,01) in Group 2, and by 152% (p<0,001) in Group 3. There was a strong positive correlation between galectin-3 and 3-nitrotyrosin and between galectin-3 and LDL oxidation across all three groups. The activity of endogenous inflammation also increased in parallel with CHF FC. A strong positive correlation between galectin-3 and hsCRP, as well as between galectin-3 and interleukin-6, was also observed.

Conclusion. Galectin-3 levels correlate with CHF severity and are associated with the key parameters of NOS and endogenous inflammationn. Therefore, galectin-3 could be regarded as a marker and mediator of these pathological processes.

1. Ageev F. G., Azizova A. G. Galectin-3 – new biomarker for heart failure. Heart failure 2011; 12:108–14. Russian (Агеев Ф. Г., Азизова А. Г. Галектин-3 – новый биохимический маркер сердечной недостаточности. Сердечная недостаточность 2011; 12:108–14).

2. de Filippi C. R., Felker G. M. Galectin-3 in heart failure-linking fibrosis, remodeling, and progression. US Cardiology 2010; 7 (1):67–70.

3. Almkvist J., Karlsson A. Galectins as inflammatory mediators. Glycocon J 2004; 19:575–81.

4. Ragino Ju. I., Voevoda M. I., Dushkin M. I. et al. Application of new biochemical methods for an estimation of oxidative-antioxidative potential of low density lipoproteins. Clinical and laboratory diagnostics 2005; 4:11–5. Russian (Рагино Ю. И., Воевода М. И., Душкин М. И. и др. Применение новых биохимических способов для оценки окислительно-антиоксидантного потенциала липопротеинов низкой плотности. Клиническая и лабораторная диагностика 2005; 4:11–5.

5. Lu Z., Xu X., Hu X. Extracellular Superoxide Dismutase Deficiency Exacerbates Pressure Overload–Induced Left Ventricular Hypertrophy and Dysfunction. Hypertension 2008; 51 (1):19–25.

6. Shah R. V., Chen-Tournoux A. A., Picard M. H. et al. Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure. Eur J Heart Fail 2010; 8:826–32.

7. Timonen P., Magga J., Risteli J. et al. Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy. Int J Cardiol. 2008; 124:293–300.

8. Boer R. A., Lok D. J., Jaarsma T. et al. Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejectionn fraction. Ann Med 2011; 43:60–8.

9. Belenkov J. N., Tatenkulova S. N., Mareev V. Ju, et al. Correlation of level of proinflammatory factors with severity of heart failure in patients with ischemic heart disease. Heart failure 2009; 10 (3):137–39. Russian (Беленков Ю. Н., Татенкулова С. Н., Мареев В. Ю. и др. Взаимосвязь уровня провоспалительных факторов с выраженностью сердечной недостаточности при ишемической болезни сердца. Сердечная недостаточность 2009; 10 (3):137–39).

10. MacKinnon A. C., Farnworth S. L., Hodkinson P. S. et al. Regulation of alternative macrophage activation by galectin-3. The J Immunology 2008; 180:2650–658.

11. Liu Y. H., D’Ambrosio M., Liao Т. О. 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; 296:404–12.

12. Boer R. A., Yu L., Veldhuisen D. J. Galectin-3 in cardiac remodeling and heart failure. Curr Heart Fail Rep 2010; 7:1–8.

13. Zhu W., Sano H., Nagai R. et all. The Role of Galectin-3 in Endocytosis of Advanced Glycation End Products and Modified Low Density Lipoproteins. Biochem Biophys Res Commun 2001; 2 (4):1183–188.

14. Suzuki Y., Inoue T., Yoshimaru T., Ra C. Galectin-3 but not galectin-1 induces mast cell death by oxidative stress and mitochondrial permeability transition. Biochim Biophys Acta 2008; 1783:924–34.

15. Molnar A., Toth A., Bagi Z. et al. Activation of the Poly (ADP-Ribose) Polymerase Pathway in Human Heart Failure. Mol Med 2006; 12 (7–8):143–52.