Interleukin-6 and Galectin-3 as biomarkers associated with chronic inflammation in patients with suspected cardiac fibrosis
DOI:
https://doi.org/10.62305/biosana.v5i5.859Keywords:
interleukin-6; galectin-3; inflammation; fibrosis; heart failureAbstract
Cardiac fibrosis is a significant structural alteration in the pathophysiology of cardiovascular diseases such as heart failure, characterized by myocardial tissue remodeling, chronic inflammation, and progression to ventricular dysfunction. Among the biomarkers involved in these processes, interleukin-6 (IL-6) and galectin-3 (Gal-3) stand out, widely studied for their role in systemic inflammation, fibroblast activation, and cardiac remodeling. The aim of this research was to analyze the recent scientific evidence on the usefulness of IL-6 and Gal-3 as biomarkers associated with chronic inflammation and cardiac fibrosis. A narrative review based on the PRISMA method was performed. A search was conducted in PubMed, the Virtual Health Library (VHL), and Web of Science between 2015 and 2024. 117 articles were identified in PubMed, 184 in the VHL, and 185 in Web of Science (n = 486). After removing duplicates (n = 188), 298 records were screened by title and abstract review. Potentially eligible articles were assessed in full text, and 28 studies meeting the clinical and methodological evaluation criteria were ultimately included. The included studies demonstrate a consistent association between elevated IL-6 levels and greater inflammatory activity, worse cardiac remodeling, and an increased risk of cardiovascular events. Similarly, elevated Gal-3 levels are associated with active myocardial fibrosis, progression of heart failure, and increased mortality. The combination of IL-6 and Gal-3 improves the predictive capacity of risk compared to individual analyses. It is concluded that IL-6 and Gal-3 represent complementary biomarkers of inflammation and cardiac fibrosis, with potential utility in risk stratification and clinical decision-making in patients with suspected myocardial remodeling.
Downloads
References
de Boer RA, De Keulenaer G, Bauersachs J, Brutsaert D, Cleland JG, Diez J, et al. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology. Eur J Heart Fail [Internet]. 2019 Mar 1 [cited 2025 Oct 27];21(3):272–85. Available from: https://doi.org/10.1002/ejhf.1406
Chute M, Aujla P, Jana S, Kassiri Z. The Non-Fibrillar Side of Fibrosis: Contribution of the Basement Membrane, Proteoglycans, and Glycoproteins to Myocardial Fibrosis. Journal of Cardiovascular Development and Disease 2019, Vol 6, Page 35 [Internet]. 2019 Sep 23 [cited 2025 Oct 27];6(4):35. Available from: https://doi.org/10.3390/jcdd6040035
Speranza Sánchez M, Adames Quintero A, Benavides Santos A, Paulino A, González B, Brenes Umaña CD, et al. TRABAJO ORIGINAL Primer Consenso Centroamericano y El Caribe de Sociedades de Cardiología para el diagnóstico y manejo de la Falla Cardíaca. Vol. 17, L. E. Echeverría Correa. 2015. Available from: https://www.scielo.sa.cr/scielo.php?script=sci_arttext&pid=S1409-41422015000100005&lng=en
Fernandez Sanchez JA, Moreira Vera JJ, Santana Lopera KL, Cedeno Medranda EF. Factors influencing heart failure in adult patients. Universidad de Ciencia y Tecnología. 2023 May 27;27(119):116–23. Available from: https://doi.org/10.47460/uct.v27i119.712
Qi R, Lin E, Song J, Wang Y, Lin L. Proteomic Insights into Cardiac Fibrosis: From Pathophysiological Mechanisms to Therapeutic Opportunities. Vol. 27, Molecules. MDPI; 2022. Available from: https://doi.org/10.3390/molecules27248784
tojanovic D, Mitic V, Stojanovic M, Milenkovic J, Ignjatovic A, Milojkovic M. The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis. Vol. 9, Frontiers in Cardiovascular Medicine. Frontiers Media S.A.; 2022. Available from: https://doi.org/10.3389/fcvm.2022.845878
Zhang H, Dhalla NS. The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease. Int J Mol Sci [Internet]. 2024;25(2). Available from: https://pubmed.ncbi.nlm.nih.gov/38256155/
Obeagu EI. Inflammatory cytokines and cardiac arrhythmias: from pathogenesis to potential therapies. Ann Med Surg (Lond) [Internet]. 2025;87(9):5607–13. Available from: https://pubmed.ncbi.nlm.nih.gov/40901119/
Ahmed R, Anam K, Ahmed H. Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases. Vol. 24, International Journal of Molecular Sciences. Multidisciplinary Digital Publishing Institute (MDPI); 2023. Available from: https://doi.org/10.3390/ijms24098116
Blanda V, Bracale UM, D DTM, Fortunato G. Galectin-3 in Cardiovascular Diseases. Int J Mol Sci [Internet]. 2020;21(23). Available from: https://doi.org/10.3390/ijms21239232
Ravassa S, López B, Treibel TA, San José G, Losada-Fuentenebro B, Tapia L, et al. Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies. Vol. 93, Molecular Aspects of Medicine. Elsevier Ltd; 2023. Available from: https://doi.org/10.1016/j.mam.2023.101194
Frangogiannis NG. Cardiac fibrosis. Vol. 117, Cardiovascular Research. Oxford University Press; 2021. p. 1450–88. Available from: https://doi.org/10.1093/cvr/cvaa324
Coromilas E, Que-Xu EC, Moore D V., 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 [Internet]. 2016 Jun 14 [cited 2025 Oct 27];16(1):1–10. Available from: https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-016-0298-z
Alter C, Henseler AS, Owenier C, Hesse J, Ding Z, Lautwein T, et al. IL-6 in the infarcted heart is preferentially formed by fibroblasts and modulated by purinergic signaling. Journal of Clinical Investigation. 2023 Jun 1;133(11). Available from: https://dx.doi.org/10.1172/JCI163799
Ahmed SA, Ismail HM, Alahmedi AB, Alahmadi FB, Muhawish AF, Alsubhi AA, et al. Decoding the Inflammatory Pathway in Heart Failure: The Role of Interleukins and Tumor Necrosis Factor-Alpha in Disease Severity. Journal of Clinical Medicine 2025, Vol 14, Page 6092 [Internet]. 2025 Aug 28 [cited 2025 Oct 27];14(17):6092. Available from: https://doi.org/10.3390/jcm14176092
Li Y, Zhao J, Yin Y, Li K, Zhang C, Zheng Y. The Role of IL-6 in Fibrotic Diseases: Molecular and Cellular Mechanisms. Vol. 18, International Journal of Biological Sciences. Ivyspring International Publisher; 2022. p. 5405–14. Available from: https://dx.doi.org/10.7150/ijbs.75876
Tiller C, Reindl M, Holzknecht M, Lechner I, Schwaiger J, Brenner C, et al. Association of plasma interleukin-6 with infarct size, reperfusion injury, and adverse remodelling after ST-elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care [Internet]. 2022 Feb 8 [cited 2025 Oct 27];11(2):113–23. Available from: https://doi.org/10.1093/ehjacc/zuab110
Ou G, Cai H, Yao K, Qiu Z, Yang Y, Chen Y, et al. Exploring the therapeutic potential of interleukin-6 receptor blockade in cardiovascular disease treatment through Mendelian randomization. Scientific Reports 2024 14:1 [Internet]. 2024 Sep 13 [cited 2025 Oct 27];14(1):1–9. Available from: https://www.nature.com/articles/s41598-024-72195-4
Hara A, Niwa M, Kanayama T, Noguchi K, Niwa A, Matsuo M, et al. Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early Stage Pathology. Biomolecules 2020, Vol 10, Page 1277 [Internet]. 2020 Sep 4 [cited 2025 Oct 27];10(9):1277. Available from: https://doi.org/10.3390/biom10091277
Sygitowicz G, Maciejak-Jastrzębska A, Sitkiewicz D. The Diagnostic and Therapeutic Potential of Galectin-3 in Cardiovascular Diseases. Biomolecules [Internet]. 2021;12(1). Available from: https://pubmed.ncbi.nlm.nih.gov/35053194/
Amin HZ, Amin LZ, Wijaya IP. Galectin-3: a novel biomarker for the prognosis of heart failure. Clujul Med [Internet]. 2017;90(2):129–32. Available from: https://pubmed.ncbi.nlm.nih.gov/28559694/
Zaborska B, Sygitowicz G, Smarż K, Pilichowska-Paszkiet E, Budaj A. Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity. Sci Rep [Internet]. 2020;10(1):16682. Available from: https://pubmed.ncbi.nlm.nih.gov/33028850/
Markousis-Mavrogenis G, Tromp J, Ouwerkerk W, Devalaraja M, Anker SD, Cleland JG, et al. The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study. Eur J Heart Fail [Internet]. 2019 Aug 1 [cited 2025 Oct 27];21(8):965–73. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.1482
Besler C, Lang D, Urban D, Rommel KP, Von Roeder M, Fengler K, et al. Plasma and cardiac galectin-3 in patients with heart failure reflects both inflammation and fibrosis: Implications for its use as a biomarker. Circ Heart Fail [Internet]. 2017 Mar 1 [cited 2025 Oct 27];10(3). Available from: https://doi.org/10.1161/CIRCHEARTFAILURE.116.003804
Zaborska B, Sikora-Frąc M, Smarż K, Pilichowska-Paszkiet E, Budaj A, Sitkiewicz D, et al. The Role of Galectin-3 in Heart Failure—The Diagnostic, Prognostic and Therapeutic Potential—Where Do We Stand? International Journal of Molecular Sciences 2023, Vol 24, Page 13111 [Internet]. 2023 Aug 23 [cited 2025 Oct 27];24(17):13111. Available from: https://doi.org/10.3390/ijms241713111
Waśkiewicz Z, Bezuglov E, Talibov O, Gajda R, Mukhambetov Z, Azerbaev D, et al. Divergent Cardiac Adaptations in Endurance Sport: Atrial Fibrillation Markers in Marathon Versus Ultramarathon Athletes. J Cardiovasc Dev Dis [Internet]. 2025;12(7). Available from: https://pubmed.ncbi.nlm.nih.gov/40710785/
Amioka N, Nakamura K, Kimura T, Ohta-Ogo K, Tanaka T, Toji T, et al. Pathological and clinical effects of interleukin-6 on human myocarditis. J Cardiol [Internet]. 2021 Aug 1 [cited 2025 Oct 27];78(2):157–65. Available from: https://www.journal-of-cardiology.com/action/showFullText?pii=S0914508721000575
Alogna A, Koepp KE, Sabbah M, Espindola Netto JM, Jensen MD, Kirkland JL, et al. Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail [Internet]. 2023 Nov 1 [cited 2025 Oct 27];11(11):1549–61. Available from: https://www.jacc.org/doi/10.1016/j.jchf.2023.06.031
Mossmann M, Wainstein MV, Mariani S, Machado GP, de Araújo GN, Andrades M, et al. Increased serum IL-6 is predictive of long-term cardiovascular events in high-risk patients submitted to coronary angiography: an observational study. Diabetol Metab Syndr [Internet]. 2022 Dec 1 [cited 2025 Oct 27];14(1):1–9. Available from: https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-022-00891-0
Florido R, Kwak L, Echouffo-Tcheugui JB, Zhang S, Michos ED, Nambi V, et al. Obesity, Galectin-3, and Incident Heart Failure: The ARIC Study. J Am Heart Assoc [Internet]. 2022;11(9): e023238. Available from: https://pubmed.ncbi.nlm.nih.gov/35491999/
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 BIOSANA Health Scientific Journal. ISSN 2960-8481
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
