Abstract. Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, highlighting the need for novel diagnostic and prognostic biomarkers. This study examines the role of fibrosis and endothelial dysfunction markers in the development of vascular damage in cardiovascular diseases. Galectin-3 and soluble suppression of tumorigenicity 2 (sST2) play crucial roles in myocardial fibrosis and vascular remodeling, with elevated levels being significant predictors of negative cardiovascular outcomes. sST2, as an antagonist of interleukin-33, promotes inflammation and fibrosis, whereas galectin-3 regulates cellular proliferation and differentiation in fibrotic processes. Additionally, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H 2 S) are essential for vascular homeostasis, preventing vascular stiffness and endothelial dysfunction. Impaired biosynthesis and reduced bioavailability of these molecules contribute to oxidative stress, vascular inflammation, and the progression of atherosclerosis. Integrating these biomarkers into clinical practice may enhance early diagnosis, improve risk stratification, and support the development of personalized therapeutic strategies for patients with cardiovascular pathology.

Keywords: cardiovascular diseases, fibrosis, endothelial dysfunction, galectin-3, sST2, nitric oxide, hydrogen sulfide, vascular remodeling

Full text: PDF (Ukr)

1. Lu Zhang, Jing Zhou, Wei Kong. Extracellular matrix in vascular homeostasis and disease, Nature Reviews Cardiology, 2025.doi.org/10.1038/s41569-024-01103-0
2. Hua R, Gao H, He C, Xin S, Wang B, Zhang S, et al. An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed. Front. Cardiovasc. Med.(2023). 10:1273502.doi.org/10.3389/fcvm.2023.1273502
3. Lin PK, Davis GE. Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence. Arterioscler Thromb Vasc Biol. 2023 Sep;43(9):1599-1616.doi.org/10.1161/ATVBAHA.123.318237
4. Zihan Ma, Chenfeng Mao. Extracellular matrix dynamics in vascular remodeling. American Journal of Physiology-Cell PhysiologyVolume 319, Issue 3 Sep 2020. Pages C457-C610.doi.org/10.1152/ajpcell.00147.2020
5. Zeyu Cai, Ze Gong, Zhiqing Li, Li Li, and Wei Kong. Vascular Extracellular Matrix Remodeling and Hypertension. Antioxidants & Redox Signaling 2021; 34:10, 765-783.doi.org/10.1089/ars.2020.8110
6. Vértes V, Porpáczy A, Nógrádi Á, Tőkés-Füzesi M, Hajdu M, Czirják L, et al. Galectin-3 and sST2: associations to the echocardiographic markers of the myocardial mechanics in systemic sclerosis - a pilot study. Cardiovasc Ultrasound. 2022 Jan 18;20(1):1.doi.org/10.1186/s12947-022-00272-7
7. 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 Sep 4;10(9):1277.doi.org/10.3390/biom10091277
8. Merino-Merino A, Gonzalez-Bernal J, Fernandez-Zoppino D, Saez-Maleta R, Perez-Rivera J.-A. The Role of Galectin-3 and ST2 in Cardiology: A Short Review. Biomolecules.2021;11:1167.doi.org/10.3390/biom11081167
9. Pokrovska N, Denysenko N, Fomenko I, Sklyarova H, Sklyarov E, Basylevych A, et al. Galectin-3 in Blood Serum and Lymphocytes as a Marker of Myocardial Damage in Patients with Arterial Hypertension and COVID-19. Anti-Inflammatory & Anti-allergy Agents in Medicinal Chemistry. 2023. 22 (4). P. 250-260.doi.org/10.2174/0118715230273606231103075632
10. Ikeda, S. Is soluble ST2 an useful biomarker for early diagnosis of coronary atherosclerosis? Hypertens Res. 2025;48, 839-841.doi.org/10.1038/s41440-024-01987-y
11. Radu-Stefan Miftode, Antoniu Octavian Petriş, Viviana Onofrei Aursulesei, Corina Cianga, et al. The Novel Perspectives Opened by ST2 in the Pandemic: A Review of Its Role in the Diagnosis and Prognosis of Patients with Heart Failure and COVID-19. Diagnostics vol. 11 issue 2. 2021; 2075-4418.doi.org/10.3390/diagnostics11020175
12. Luca Marino, Antonio Concistrè, Marianna Suppa, Gioacchino Galardo, Antonello Rosa, Giuliano Bertazzoni, et al. Prognostic Role of sST2 in Acute Heart Failure and COVID-19 Infection-A Narrative Review on Pathophysiology and Clinical Prospective. 2022; 1422-0067.doi.org/10.3390/ijms23158230
13. Федевич Ю. І., Денисенко Н. В., Фоменко У. О., Склярова О. Є., Скляров Є. Я., Кобилінська Л. І. Зміни концентрації sST2, активності мієлопероксидази та iндуцибельної NO-синтази в сироватці крові та лімфоцитах як показник важкості перебігу захворювання у пацієнтів з артеріальною гіпертензією та на тлі коронавірусної хвороби. Експериментальна та клінічна фізіологія і біохімія. 2024. Т. 100, вип. 2. С. 20-29.doi.org/10.25040/ecpb2024.02.020
14. Rabkin SW, Tang JKK. The utility of growth differentiation factor-15, galectin-3, and sST2 as biomarkers for the diagnosis of heart failure with preserved ejection fraction and compared to heart failure with reduced ejection fraction: a systematic review. Heart Fail Rev 26. 2021;799-812.doi.org/10.1007/s10741-020-09913-3
15. Jianhong Sun, Yuanwei Xu, Yang Wu, Jiayu Sun, Geng Yin, Yucheng Chen, et al. The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement, Rheumatology, Volume 63, Issue 4, April 2024. Pages 172-1179.doi.org/10.1093/rheumatology/kead182
16. Giuseppe Vergaro, Francesco Gentile, Alberto Aimo, James L. Januzzi Jr, A. Mark Richards, et al. Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. Men with chronic heart failure. ESC Heart Failure 2022; 9:2084-209.doi.org/10.1002/ehf2.13883
17. Junpei Li, Tianyu Cao, Yaping Wei, Nan Zhang, Ziyi Zhou, Zhuo Wang, et al. A Review of Novel Cardiac Biomarkers in Acute or Chronic Cardiovascular Diseases: The Role of Soluble ST2, Lipoprotein- Associated Phospholipase A2, Myeloperoxidase and Procalcitonin. Hindawi Disease Markers 2021,6258865,10.doi.org/10.1155/2021/6258865
18. N. K. POKROVSKA, H. E. SKLYAROVA, N. V. DENYSENKO, I. S. FOMENKO, E. Y. SKLYAROV, L. I. KOBYLINSKA. Prognostic value of sST2 and vWF determination in blood serum in patients with arterial hypertension and covid-19. Experimental and Clinical Physiology and Biochemistry. 2023. Т. 97, вип. 3. С. 5-13.doi.org/10.25040/ecpb2023.03.005
19. Sun H-J, Wu Z-Y, Nie X-W and Bian J-S. Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide. Front. Pharmacol.2020;10:1568.doi.org/10.3389/fphar.2019.01568
20. Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int J Mol Sci. 2021 Apr 8;22(8):3850.doi.org/10.3390/ijms22083850
21. Lee Bockus, Francis Kim. Coronary endothelial dysfunction: from pathogenesis to clinical implications: Open Heart 2022;9:e002200. doi.org/10.1136/openhrt-2022-002200
22. Shaito A, Aramouni K, Assaf R, Parenti A, Orekhov A, Yazbi AE, et al. Oxidative Stress-Induced Endothelial Dysfunction in Cardiovascular Diseases. Front Biosci (Landmark Ed). 2022 Mar 18;27(3):105.doi.org/10.31083/j.fbl2703105
23. Giovanna Scioli M, D'Amico F, Rodríguez Guzmán R, Céspedes Miranda EM, Orlandi A. Oxidative Stress-Induced Endothelial Dysfunction Contributes To Cardiovascular Disease. Rev Cubana Inv Bioméd 2019;38 (1). revibiomedica.sld.cu/index.php/ibi/article/view/168
24. Abdullah Shaito, Karl Aramouni, Roland Assaf, Astrid Parenti, Alexander Orekhov, Ahmed El Yazbi, et al. Oxidative Stress-Induced Endothelial Dysfunction in Cardiovascular Diseases. Front. Biosci. (Landmark Ed) 2022, 27(3), 105.doi.org/10.31083/j.fbl2703105
25. Wang X, He B. Endothelial dysfunction: molecular mechanisms and clinical implications.MedComm (2020). 2024 Jul 22;5(8):e651.doi.org/10.1002/mco2.651
26. Huang Y, Song C, He J and Li M. Research progress in endothelial cell іnjury and repair. Front. Pharmacol. 2022;13:997272.doi.org/10.3389/fphar.2022.997272
27. Landry AP, Roman J, Banerjee R. Structural perspectives on H2S homeostasis. CurrOpin Struct Biol. 2021;71:27-35.doi.org/10.1016/j.sbi.2021.05.010
28. I. S. FOMENKO, T. I. BONDARCHUK Hydrogen sulfide: biological and pathochemistry. Experimental and Clinical Physiology and Biochemistry. 2024; 99(1). С. 1-15.doi.org/10.25040/ecpb2024.01.005
29. Yang Y-W, Deng N-H, Tian K-J, Liu L-S, Wang Z, Wei D-H, et al. Development of hydrogen sulfide donors for anti-atherosclerosis therapeutics research: Challenges and future priorities. Front. Cardiovasc. Med. 2022; 9:909178.doi.org/10.3389/fcvm.2022.909178
30. Valentina Citi, Alma Martelli, Era Gorica, Simone Brogi, Lara Testai, Vincenzo Calderone. Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches, Journal of Advanced Research, Volume 27, 2021. Pages 99-113.doi.org/10.1016/j.jare.2020.05.015
31. Xiao, Lina, Dong, Jing-Huia, Teng, Xua, Jin, Shenga, Xue, Hong-Meia, Liu, Shang-Yuc, et al. Hydrogen sulfide improves endothelial dysfunction in hypertension by activating peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase signaling. Journal of Hypertension 36(3):p 651-665, March 2019.doi.org/10.1097/HJH.0000000000001605
32. Zhu C, Liu Q, Li X, Wei R, Ge T, Zheng X, Li B, Liu K and Cui R. Hydrogen sulfide: A new therapeutic target in vascular diseases. Front. Endocrinol. 2022;13:934231.doi.org/10.3389/fendo.2022.934231
33. Ciccone V, Genah S, Morbidelli L. Endothelium as a Source and Target of H2S to Improve Its Trophism and Function. Antioxidants. 2021, 10, 486.doi.org/10.3390/antiox10030486
34. Cinelli MA, Do HT, Miley GP, Silverman RB. Inducible nitric oxide synthase: Regulation, structure, and inhibition. Med Res Rev. 2020 Jan;40(1):158-189.doi.org/10.1002/med.21599
35. Wilmes V, Kur IM, Weigert A, Verhoff MA, Gradhand E, Kauferstein S. iNOS expressing macrophages co-localize with nitrotyrosine staining after myocardial infarction in humans. Front Cardiovasc Med. 2023 Mar 30;10:1104019.doi.org/10.3389/fcvm.2023.1104019