Features of angiogenesis as a component of reparative regeneration in diabetes mellitus
https://doi.org/10.14341/omet13086
Abstract
Diabetes mellitus is one of the most pressing problems of modern medicine, characterized by high morbidity (with continuous growth), a decrease in the duration and quality of life, numerous and severe complications. Among the disorders observed in diabetes mellitus, the insufficiency of angiogenesis, the process of formation of new vessels from existing ones, is noted. This process plays an important role in reparative regeneration, ensuring the formation of granulation tissue. The insufficiency of angiogenesis in diabetes mellitus causes a decrease in the rate and quality of wound healing in such patients. We conducted a literature review with the following objectives: to collect up-to-date data on the mechanisms of angiogenesis and its regulation, to identify the links of angiogenesis that are subject to the pathological influence of diabetes mellitus; and to identify potential targets of pharmacological therapy that can compensate for this effect. The results of this work will allow us to apply the data obtained in studies aimed at developing a personalized approach to the management of patients with diabetes mellitus.
About the Authors
K. S. MadonovFederal State Budgetary Educational Institution of Higher Education "National Research Ogarev Mordovia State University"
Russian Federation
Konstantin S. Madonov
268 Sadovaya street, 430910 Saransk, Luhovk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
Ya. A. Danilova
Russian Federation
Yana A. Danilova
Saransk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
I. V. Kamalikhin
Russian Federation
Ilya V. Kamalikhin
Saransk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
D. G. Sardaeva
Russian Federation
Dar’ya G. Sardaeva
Saransk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
T. I. Vlasova
Russian Federation
Tat'yana I. Vlasova, MD, Associated professor
Saransk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
References
1. Standarts of specialized diabetes care, 10th edition (revised). Ed by Dedov II, Shestakova MV, Mayorov AYu. Sakharnyi diabet. 2021;24(1S):1-148. (In Russ.) doi: https://doi.org/10.14341/DM12802
2. Komelyagina EYu, Antsiferov MB. Wound healing in diabetic foot patients. Endokrinologiya: novosti, mneniya, obuchenie. 2018;7(4):42-47. (In Russ.) doi: https://doi.org/10.24411/2304-9529-2018-14005
3. Pronina EA, Stepanova TV, Kiriyazi TS, et al. Features of angogenesis in skin tissue regeneration (review). Saratovskii nauchno-meditsinskii zhurnal. 2019;15(1):104-107. (In Russ.)
4. Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomedicine & Pharmacotherapy. 2019;112:108615. doi: https://doi.org/10.1016/j.biopha.2019.108615
5. Kurtukova MO, Bugaeva IO, Ivanov AN. Factors regulating angiogenesis. Sovremennye problemy nauki i obrazovaniya. 2015;5. (In Russ.)
6. Yudina AYu, Bogdanov-ml. AA, Pirogov YuA. Magnitno-rezonansnaya tomografiya v izuchenii angiogeneza i ego molekulyarnykh markerov. Ed by Pirogov YuA. Moscow: Fizicheskii fakul'tet MGU imeni M.V. Lomonosova; 2008. (In Russ.)
7. Chouinard-Pelletier G, Jahnsen ED, Jones EA. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development. Angiogenesis. 2013;16(1):71-83. doi: https://doi.org/10.1007/s10456-012-9300-2
8. Galie PA, Nguyen DH, Choi CK et al. Fluid shear stress threshold regulates angiogenic sprouting. Proceedings of the National Academy of Sciences. 2014;111(22):7968-73. doi: https://doi.org/10.1073/pnas.1310842111
9. Zhang Z, Yao L, Yang J et al. PI3K/Akt and HIF 1 signaling pathway in hypoxia ischemia (Review). Molecular Medicine Reports. 2018;18(4):3547-3554. doi: https://doi.org/10.3892/mmr.2018.9375
10. Apte RS, Chen DS, Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019;176(6):1248-1264. doi: https://doi.org/10.1016/j.cell.2019.01.021
11. Liu Y, Liu Y, Deng J, et al. Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects. Frontiers in Endocrinology (Lausanne). 2021;12:744868. doi: https://doi.org/10.3389/fendo.2021.744868
12. Lee HJ, Hong YJ, Kim M. Angiogenesis in Chronic Inflammatory Skin Disorders. International Journal of Molecular Sciences. 2021;22(21):12035. doi: https://doi.org/10.3390/ijms222112035
13. Akwii RG, Sajib MS, Zahra FT, Mikelis CM. Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology. Cells. 2019;8(5):471. doi: https://doi.org/10.3390/cells8050471
14. Isidori AM, Venneri MA; Fiore D. Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: Therapeutic strategies to restore the highs and lows of angiogenesis in diabetes. Journal of Endocrinological Investigation. 2016;39(11): 1235–1246. doi: https://doi.org/10.1007/s40618-016-0502-0
15. Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Medicinal Research Reviews. 2003;23(2):117-45. doi: https://doi.org/10.1002/med.10024
16. Guan Y, Niu H, Liu Z et al. Sustained oxygenation accelerates diabetic wound healing by promoting epithelialization and angiogenesis and decreasing inflammation. Science Advances. 2021;7(35):eabj0153. doi: https://doi.org/10.1126/sciadv.abj0153
17. Vlasov TD, Nesterovich II, Shimanski DA. Endothelial dysfunction: from the particular to the general. Return to the «Old Paradigm»? Regionarnoe krovoobrashchenie i mikrotsirkulyatsiya. 2019;18(2):19–27. (In Russ.) doi: https://doi.org/10.24884/1682-6655-2019-18-2-19-27
18. Popyhova EB, Stepanova TV, Lagutina DD et al. The Role of Diabetes in the Onset and Development of Endothelial Dysfunction. Problemy endokrinologii. 2020;66(1):47-55. (In Russ.) doi: https://doi.org/10.14341/probl1221
19. Mel'nikova YuS, Makarova TP. Endothelial dysfunction as the key link of chronic diseases pathogenesis. Kazanskii meditsinskii zhurnal. 2015;96(4):659-665. (In Russ.) doi: https://doi.org/10.17750/KMJ2015-659
20. Vlasova TI, Petrishchev NN, Vlasov TD. Endothelial dysfunction as the typical pathological state. Regionarnoe krovoobrashchenie i mikrotsirkulyatsiya. 2022;21(2):4–15. (In Russ.) doi: https://doi.org/10.24884/1682-6655-2022-21-2-4-15
21. Eelen G, de Zeeuw P, Simons M, Carmeliet P. Endothelial cell metabolism in normal and diseased vasculature. Circulation Research. 2015;116(7):1231-1244. doi: https://doi.org/10.1161/CIRCRESAHA.116.302855
22. Shi Y, Vanhoutte PM. Macro- and microvascular endothelial dysfunction in diabetes. Journal of Diabetes. 2017;9(5):434-449. doi: https://doi.org/10.1111/1753-0407.12521
23. Kirilyuk ML, Ishchenko VA. Pathogenesis of diabetic retinopathy: a literature review. Mezhdunarodnyi endokrinologicheskii zhurnal. 2019;15(7):567-575. (In Russ.) doi: https://doi.org/10.22141/2224-0721.15.7.2019.186061
24. Okonkwo UA, DiPietro LA. Diabetes and Wound Angiogenesis. International Journal of Molecular Sciences. 2017;18(7):1419. doi: https://doi.org/10.3390/ijms18071419
25. Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Translational Research. 2021;236:109-116. doi: https://doi.org/10.1016/j.trsl.2021.05.006
26. Sharifiaghdam M, Shaabani E, Faridi-Majidi R et al. Macrophages as a therapeutic target to promote diabetic wound healing. Molecular Therapy. 2022;30(9):2891-2908. doi: https://doi.org/10.1016/j.ymthe.2022.07.016
27. Basu Mallik S, Jayashree BS, Shenoy RR. Epigenetic modulation of macrophage polarization - perspectives in diabetic wounds. Journal of Diabetes and its Complications. 2018;32(5):524-530. doi: https://doi.org/10.1016/j.jdiacomp.2018.01.015
28. Okizaki S, Ito Y, Hosono K et al. Suppressed recruitment of alternatively activated macrophages reduces TGF-β1 and impairs wound healing in streptozotocin-induced diabetic mice. Biomedicine & Pharmacotherapy. 2015;70:317-25. doi: https://doi.org/10.1016/j.biopha.2014.10.020
29. Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunological Reviews. 2018;282(1):121-150. doi: https://doi.org/10.1111/imr.12634
30. Zhou K, Ma Y, Brogan MS. Chronic and non-healing wounds: The story of vascular endothelial growth factor. Medical Hypotheses. 2015;85(4):399-404. doi: https://doi.org/10.1016/j.mehy.2015.06.017
31. Malone-Povolny MJ, Maloney SE, Schoenfisch MH. Nitric Oxide Therapy for Diabetic Wound Healing. Advanced Healthcare Materials. 2019;8(12):e1801210. doi: https://doi.org/10.1002/adhm.201801210
32. Honing ML, Morrison PJ, Banga JD et al. Nitric oxide availability in diabetes mellitus. Diabetes / Metabolism Reviews. 1998; 14(3):241-249. doi: https://doi.org/10.1002/(sici)1099-0895(1998090)14:3<241::aid-dmr216>3.0.co;2-r
33. Beer HD, Longaker MT, Werner S. Reduced expression of PDGF and PDGF receptors during impaired wound healing. Journal of Investigative Dermatology. 1997;109(2):132–138. doi: https://doi.org/10.1111/1523-1747.ep12319188
34. Brown RL, Breeden MP, Greenhalgh DG. PDGF and TGF-α act synergistically to improve wound healing in the genetically diabetic mouse. Journal of Surgical Research. 1994;56(6):562–570. doi: https://doi.org/10.1006/jsre.1994.1090
35. Icli B, Nabzdyk CS, Lujan-Hernandez J et al. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a. Journal of Molecular and Cellular Cardiology. 2016;91:151–159. doi: https://doi.org/10.1016/j.yjmcc.2016.01.007
36. Veith AP, Henderson K, Spencer A et al. Therapeutic strategies for enhancing angiogenesis in wound healing. Advanced Drug Delivery Reviews. 2019;146:97-125. doi: https://doi.org/10.1016/j.addr.2018.09.010
37. Xu J, Zgheib C, Hu J et al. The role of microRNA-15b in the impaired angiogenesis in diabetic wounds. Wound Repair and Regeneration. 2014;22(5):671–677. doi: https://doi.org/10.1111/wrr.12217
38. Burgess JL, Wyant WA, Abdo Abujamra B et al. Diabetic Wound-Healing Science. Medicina (Kaunas). 2021;57(10):1072. doi: https://doi.org/10.3390/medicina57101072
39. Shestakova V.G. Stimulated angiogenesis and its role in reparative skin regeneration. Zhurnal anatomii i gistopatologii. 2018;7(3):117-124. (In Russ.) doi: https://doi.org/10.18499/2225-7357-2018-7-3-117-124
40. Sivan-Loukianova E, Awad OA, Stepanovic V et al. CD34+ blood cells accelerate vascularization and healing of diabetic mouse skin wounds. Journal of Vascular Research. 2003;40(4):368-377. doi: https://doi.org/10.1159/000072701
41. Fujita Y, Kawamoto A. Therapeutic Angiogenesis Using Autologous CD34-Positive Cells for Vascular Diseases. Annals of Vascular Diseases. 2022; 15(4):241-252. doi: https://doi.org/10.3400/avd.ra.22-00086
42. Zhou Y, Liu G, Huang H, Wu J. Advances and impact of argininebased materials in wound healing. Journal of Materials Chemistry B. 2021; 9(34):6738-6750. doi: https://doi.org/10.1039/d1tb00958c
43. Buraschi S, Neill T, Goyal A et al. Decorin causes autophagy in endothelial cells via Peg3. Proceedings of the National Academy of Sciences (USA). 2013;110(28):2582-2591. doi: https://doi.org/10.1073/pnas.1305732110
44. Niu C, Chen Z, Kim KT et al. Metformin alleviates hyperglycemiainduced endothelial impairment by downregulating autophagy via the Hedgehog pathway. Autophagy. 2019;15(5):843-870. doi: https://doi.org/10.1080/15548627.2019.1569913
Review
For citations:
Madonov K.S., Danilova Ya.A., Kamalikhin I.V., Sardaeva D.G., Vlasova T.I. Features of angiogenesis as a component of reparative regeneration in diabetes mellitus. Obesity and metabolism. 2026;23(2):106-113. (In Russ.) https://doi.org/10.14341/omet13086
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