DRUG CORRECTION OF GLYCOCALYX DISORDERS IN COMPLICATIONS OF DIABETES MELLITUS
https://doi.org/10.52485/19986173_2025_3_118
Abstract
Diabetes mellitus (DM) is a common endocrine disorder that can lead to various complications, including cardiovascular diseases, nephropathy, and neuropathy. These complications are associated with damage to the endothelial glycocalyx (EG), which is a layer of carbohydrates that covers the surface of endothelial cells and plays an important role in maintaining vascular integrity and regulating inflammation. In recent years, researchers have shown interest in targeting EG as a potential treatment for DM complications. This article will discuss existing approaches and medications that can affect EG, based on recent studies.
About the Authors
A. P. Vorobyeva
Stavropol State Medical University; City Children's Clinical Hospital named after G.K. Filippsky
Russian Federation
Russian Federation
Vorobyeva A.P., anesthesiologist-resuscitator of the Intensive Care and Intensive Care Wards, Assistant of the Department of Emergency Medical Care with a course of Additional Postgraduate Education
310 Mira St., Stavropol, 355017
5 Ponomareva St., Stavropo'l, 355002
Yu. V. Bykov
Stavropol State Medical University
Russian Federation
Russian Federation
Bykov Yu.V., Candidate of Medical Sciences, Associate Professor of the Department of Anesthesiology, Resuscitation and Emergency Medicine
310 Mira St., Stavropol, 355017
V. A. Baturin
Stavropol State Medical University
Russian Federation
Russian Federation
Baturin V.A., Doctor of Medical Sciences, Professor, Head of the Department of Clinical Pharmacology, with a course of Additional Postgraduate Education
310 Mira St., Stavropol, 355017
V. V. Massorov
City Children's Clinical Hospital named after G.K. Filippsky
Russian Federation
Russian Federation
Massorov V.V., anesthesiologist-resuscitator of the Intensive Care and Intensive Care Wards
5 Ponomareva St., Stavropo'l, 355002
References
1. Harreiter J., Roden M. Diabetes mellitus – Definition, Klassifikation, Diagnose, Screening und Prävention. Wien Klin Wochenschr. 2023. 135: 7–17. doi:10.1007/s00508-022-02122-y.
2. American Diabetes Association. 2. Classification and Diagnosis of Diabetes. Diabetes Care. 2020. 43: 14– 31. doi:10.2337/dc20-S002.
3. Rosen C., Ingelfinger J. Traveling down the long road to type 1 diabetes mellitus prevention. N Engl J Med. 2019. 381 (7): 666–667. doi:10.1056/NEJMe1907458.
4. Wei J., Tian J., Tang C., et al. The Influence of Different Types of Diabetes on Vascular Complications. J Diabetes Res. 2022. 2022: 3448618. doi:10.1155/2022/3448618.
5. Dedov I.I., Shestakova M.V., Vikulova O.K., et al. Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Diabetes Register for 2010-2022. Sakharnyy Diabet. 2023. 26 (2): 104–123. doi:10.14341/DM13035. In Russian.
6. Li H., Lu W., Wang A., et al. Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: estimates from Global Burden of Disease 2017. J Diabetes Investig. 2021. 12 (3): 346–356. doi:10.1111/jdi.13355.
7. Cole J., Florez J. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020. 16 (7): 377–390. doi:10.1038/s41581-020-0278-5.
8. Pykhova E.B., Stepanova T.V., Lagutina D.D., et al. The role of diabetes mellitus in the occurrence and development of endothelial dysfunction. Probl Endokrinol (Mosk). 2020. 66 (1): 47–55. In Russian.
9. Thota L., Chignalia A. The role of the glypican and syndecan families of heparan sulfate proteoglycans in cardiovascular function and disease. Am J Physiol Cell Physiol. 2022. 323 (4): 52–60. doi:10.1152/ajpcell.00018.2022.
10. Shurer C., Kuo J., Roberts L., et al. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Cell. 2019. 177 (7): 1757–1770. doi:10.1016/j.cell.2019.04.017.
11. Vorobyeva A.P., Bykov Yu.V., Baturin V.A., et al. (2024). Glycocalyx impairment in critical conditions: pathophysiological and clinical aspects. Yakut Medical Journal, (1) 85, 77–81. In Russian.
12. Vorobyeva A.P., Bykov Yu.V., Baturin V.A., et al. (2024). The role of the glycocalyx in the pathogenesis of diabetes mellitus complications. Transbaikal Medical Bulletin, 2, 80-89. In Russian.
13. Iliff A., Xu X.Z.S. A mechanosensitive GPCR that detects the bloody force. Cell. 2018. 173 (3): 542–544. doi:10.1016/j.cell.2018.04.001.
14. Krüger-Genge A., Blocki A., Franke R.P., et al. Vascular endothelial cell biology: An update. Int J Mol Sci. 2019. 20 (18): 4411. doi:10.3390/ijms20184411.
15. Fan J., Sun Y., Xia Y., et al. Endothelial surface glycocalyx (ESG) components and ultra-structure revealed by stochastic optical reconstruction microscopy (STORM). Biorheology. 2019. 56: 77–88. doi:10.3233/BIR-180204.
16. Suzuki A., Tomita H., Okada H. Form follows function: the endothelial glycocalyx. Transl Res. 2022. 247: 158–167. doi:10.1016/j.trsl.2022.03.014.
17. Wang G., Tiemeier G., van den Berg B.M., et al. Endothelial Glycocalyx Hyaluronan: Regulation and Role in Prevention of Diabetic Complications. Am J Pathol. 2020. 190 (4): 781–790. doi:10.1016/j.ajpath.2019.07.022.
18. Vorobyeva A.P., Bykov Yu.V., Baturin V.A., et al. (2023). Markers of glycocalyx damage in diabetes mellitus complications. Modern Problems of Science and Education, (4), 145. In Russian.
19. van den Berg B.M., Wang G., Boels M., et al. Glomerular Function and Structural Integrity Depend on Hyaluronan Synthesis by Glomerular Endothelium. J Am Soc Nephrol. 2019. 30 (10): 1886–1897. doi:10.1681/ASN.2019020192.
20. Queisser K., Mellema R., Petrey A. Hyaluronan and its receptors as regulatory molecules of the endothelial interface. J Histochem Cytochem. 2021. 69 (1): 25–34. doi:10.1369/0022155420954296.
21. Wang G., Kostidis S., Tiemeier G., et al. Shear Stress Regulation of Endothelial Glycocalyx Structure Is Determined by Glucobiosynthesis. Arterioscler Thromb Vasc Biol. 2020. 40 (2): 350–364. doi:10.1161/ATVBAHA.119.313399.
22. Hirota T., Levy J., Iba T. The influence of hyperglycemia on neutrophil extracellular trap formation and endothelial glycocalyx damage in a mouse model of type 2 diabetes. Microcirculation. 2020. 27: e12617. doi:10.1111/micc.12617.
23. Aggarwal H., Pathak P., Kumar Y., et al. Modulation of insulin resistance, dyslipidemia and serum metabolome in iNOS knockout mice following treatment with nitrite, metformin, pioglitazone, and a combination of ampicillin and neomycin. Int J Mol Sci. 2021. 23 (1): 195. doi:10.3390/ijms23010195.
24. Vorobyeva A.P., Bykov Yu.V., Baturin V.A., Muravyeva A.A. (2023). Pharmacological correction of glycocalyx injuries. Transbaikal Medical Bulletin, (2), 131–140. In Russian.
25. Ding Y., Zhou Y., Ling P., et al. Metformin in cardiovascular diabetology: A focused review of its impact on endothelial function. Theranostics. 2021. 11: 9376–9396. doi:10.7150/thno.64706.
26. DeFronzo R., Reeves W., Awad A.S. Pathophysiology of diabetic kidney disease: Impact of SGLT2 inhibitors. Nat Rev Nephrol. 2021. 17: 319–334. doi:10.1038/s41581-021-00393-8.
27. Heerspink H., Perco P., Mulder S., et al. Canagliflozin reduces inflammation and fibrosis biomarkers: A potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia. 2019. 62: 1154–1166. doi:10.1007/s00125-019-4859-4.
28. Chang M., Liu G., Wang Y., et al. Long non-coding RNA LINC00299 knockdown inhibits ox-LDLinduced T/G HA-VSMC injury by regulating miR-135a-5p/XBP1 axis in atherosclerosis. Panminerva Med. 2022. 64: 38–47. doi:10.23736/S0031-0808.20.03942-7.
29. Targosz-Korecka M., Malek-Zietek K.E., Kloska D., et al. Metformin attenuates adhesion between cancer and endothelial cells in chronic hyperglycemia by recovery of the endothelial glycocalyx barrier. Biochim Biophys Acta Gen Subj. 2020. 1864 (4): 129533. doi:10.1016/j.bbagen.2020.129533.
30. Dogné S., Flamion B., Caron N. Endothelial Glycocalyx as a Shield Against Diabetic Vascular Complications: Involvement of Hyaluronan and Hyaluronidases. Arterioscler Thromb Vasc Biol. 2018. 38 (7): 1427–1439. doi:10.1161/ATVBAHA.118.310839.
31. Gamez M., Elhegni H.E., Fawaz S. Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes. Cardiovasc Diabetol. 2024. 23: 50. doi:10.1186/s12933-024-02133-1.
32. Amjad M.V. Dendrimers in targeted delivery of anticancer drugs: achievements, problems and prospects for further research. Pharm Pharmacol. 2021;1.
33. Machin D., Trott D., Gogulamudi V., et al. Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction. Geroscience. 2023. Online ahead of print. doi:10.1007/s11357-023-00745-1.
34. Carroll B.J., Piazza G., Goldhaber S.Z. Sulodexide in venous disease. J Thromb Haemost. 2019. 17 (1): 31–38. doi:10.1111/jth.14324.
35. Roshan-Milani S., Khalilpour J., Abdollahzade F.A. The heparanase inhibitor (sulodexide) decreases urine glycosaminoglycan excretion and mitigates functional and histological renal damages in diabetic rats. Acta Med Bulg. 2019. 46 (2): 41–46. doi:10.2478/amb-2019-0017.
36. Li T., Liu C. Sulodexide recovers endothelial function through reconstructing glycocalyx in the ballooninjury rat carotid artery model. Int Angiol. 2018. 37: 72.
37. Song J.W., Zullo J.A., Liveris D., et al. Therapeutic restoration of endothelial glycocalyx in sepsis. J Pharmacol Exp Ther. 2017. 361 (1): 115–121. doi:10.1124/jpet.116.239509.
38. Ligi D., Benitez S., Croce L., et al. Electronegative LDL induces MMP-9 and TIMP-1 release in monocytes through CD14 activation: inhibitory effect of glycosaminoglycan sulodexide. Biochim Biophys Acta Mol Basis Dis. 2018. 1864 (12): 3559–3567. doi:10.1016/j.bbadis.2018.09.022.
39. De Felice F., Megiorni F., Pietrantoni I., et al. Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program. Eur Rev Med Pharmacol Sci. 2019. 23 (6): 2669-2680. doi:10.26355/eurrev_201903_17415.
40. Giurdanella G., Lazzara F., Caporarello N., et al. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE. Biochem Pharmacol. 2017. 142: 145–154. doi:10.1016/j.bcp.2017.06.130.
41. Matuska J., Benova K. Development of wall stiffness parameters in diabetes mellitus type II—evaluation of therapeutic effect of sulodexide vs naftidrofuryl: an open controlled 2-year study. Vasa-Eur J Vasc Med. 2017. 46: 30. doi:10.1024/0301-1526/a000651.
42. Sokologorsky S.V., Ovechkin A.M., Politov M.E., Bulanova E.L. Restore glycocalyx! Are there any possibilities? Anesteziol Reanimatol. 2022. 1: 102–110. doi:10.17116/anaesthesiology2022011102. In Russian.
43. Bignamini A.A., Chebil A., Gambaro G., Matuška J. Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis. Adv Ther. 2021. 38 (3): 1483–1513. doi:10.1007/s12325-021-01620-1.
44. Li Z., Wu N., Wang J., et al. Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase 2: A new therapy target in glycocalyx shedding. Br J Pharmacol. 2024. 181 (9): 1404–1420. doi:10.1111/bph.16288.
45. Zahan M.S., Hasan A., Rahman M.H., et al. Protective effects of fucoidan against kidney diseases: Pharmacological insights and future perspectives. Int J Biol Macromol. 2022. 209 (Pt B): 2119–2129. doi:10.1016/j.ijbiomac.2022.04.192.
46. Heimerl M., Sieve I., Ricke-Hoch M., et al. Neuraminidase-1 promotes heart failure after ischemia/reperfusion injury by affecting cardiomyocytes and invading monocytes/macrophages. Basic Res Cardiol. 2020. 115: 62.
47. Foote C., Ramirez-Perez F., Smith J., et al. Neuraminidase inhibition improves endothelial function in diabetic mice. Am J Physiol Heart Circ Physiol. 2023. 325 (6): 1337–1353. doi:10.1152/ajpheart.00337.2023.
48. Guo Z., Tuo H., Tang N., et al. Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. Int J Biol Sci. 2022. 18 (2): 826–840. doi:10.7150/ijbs.65938.
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Vorobyeva A.P., Bykov Yu.V., Baturin V.A., Massorov V.V. DRUG CORRECTION OF GLYCOCALYX DISORDERS IN COMPLICATIONS OF DIABETES MELLITUS. Transbaikalian Medical Bulletin. 2025;(3):118-128. (In Russ.) https://doi.org/10.52485/19986173_2025_3_118
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