VEGF-A expression in fat grafts (experimental study)

The study of vascularization of fat implants is focused on the assessment of specific external and/or internal factors affecting its stimulation.

The aim. To study the vascular bed density and VEGF-A expression in various fat grafts during lipofilling in rats at mid and late postoperative periods.

Materials and methods. The study was conducted on 65 sexually mature male Wistar rats. VEGF-A expression in recipient tissues and fat grafts was assessed on days 30, 90 and 180 after lipofilling modeling in biological objects: transplantation in the withers area on an area of 1 cm² of solid fat graft (3x4x2 mm), crushed fat grafts (1x2x2 mm) and homogenized fat (0.05 ml).

Results. Transplantation of a solid graft larger than 3x3x3 mm results in necrotic changes due to ischemia and hypoxia; leukocyte infiltration and inflammatory phenomena persist 1 month after transplantation. Maximum VEGF-A expression and higher microvessel density were observed in groups of animals with a solid graft and crushed fat grafts compared to homogenized fat in a Luer-Lock syringe. Vascularization of homogenized fat is less intense compared to fat grafts.

Conclusion. VEGF-A expression in the center of a solid fat graft reaches its maximum on the 30th postoperative day. A decrease in VEGF-A protein expression in a solid graft 6 months after autotransplantation indicates normalization of hemoperfusion of its central sections. In the third month after lipofilling, an active process of neoangiogenesis occurs on the periphery of small fat grafts. Vascularization of homogenized fat occurs with less intensity and does not differ from the physiological vascularization of normal adipose tissue.

1. Levitskaya MG, Kochneva IS, Korableva NP, Gretskova EE. Lipofilling for false varus deformity of the lower legs. Plastic Surgery and Aesthetic Medicine. 2023; (3): 61-70. (In Russ.). doi: 10.17116/plast.hirurgia202303161

2. Kato H, Mineda K, Eto H, Doi K, Kuno S, Kinoshita K, et al. Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg. 2014; 133(3): 303e–313e. doi: 10.1097/PRS.0000000000000066

3. Istranov AL, Lyubchenko AV, Isakova YuI, Mkhitaryan OA, Arutyunyan EG. Feminization of the middle third of the face. Head and neck. Russian magazine = Head and neck. Russian Journal. 2022; 10(2): 78–84. doi: 10.25792/HN.2022.10.2.78-84

4. Yang F, Li Z, Cai Z, He Y, Ke C, Wang J, et al. Pluronic F-127 Hydrogel Loaded with Human Adipose-Derived Stem Cell-Derived Exosomes Improve Fat Graft Survival via HIF-1α-Mediated Enhancement of Angiogenesis. Int J Nanomedicine. 2023; 18: 6781-6796. doi: 10.2147/IJN.S435106

5. Borkar R, Wang X, Zheng D, Miao Z, Zhang Z, Li E, et al. Human ESC-derived MSCs enhance fat engraftment by promoting adipocyte reaggregation, secreting CCL2 and mobilizing macrophages. Biomaterials. 2021; 272: 120756. doi: 10.1016/j.biomaterials.2021.120756

6. Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, et al. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes. 2018; 67(2): 235–247. doi: 10.2337/db17-0356

7. Seah I, Zhao X, Lin Q, et al. Use of biomaterials for sustained delivery of anti‐VEGF to treat retinal diseases. Eye. 2020; 34(8): 1341‐1356. doi: 10.1038/s41433-020-0770-y

8. Saikia Q, Reeve H, Alzahrani A, Critchley WR, Zeqiraj E, Divan A, et al. VEGFR endocytosis: Implications for angiogenesis. Prog Mol Biol Transl Sci. 2023; 194: 109-139. doi: 10.1016/bs.pmbts.2022.06.021

9. Konenkov VI, Nimaev VV, Shevchenko AV, Prokofiev VF. Polymorphism of angiogenesis regulation factor genes (VEGF/VEGFR), and extracellular matrix remodeling genes (MMP/TIMP), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2024; 28(4): 433-442. (In Russ.). doi: 10.18699/vjgb-24-49

10. Shevchenko AV, Prokofyev VF, Konenkov VI, Khapaev RS, Nimaev VV. Polymorphism of vascular endothelial growth factor gene (VEGF) and matrix metalloproteinase (ММР) genes in primary limb lymphedema. Medical Immunology (Russia)/Meditsinskaya Immunologiya. 2020; 22(3): 497-506. (In Russ.). doi: 10.15789/1563-0625-POV-1913

11. Yu F, Witman N, Yan D, Zhang S, Zhou M, Yan Y, et al. Human adipose-derived stem cells enriched with VEGF-modified mRNA promote angiogenesis and long-term graft survival in a fat graft transplantation model. Stem Cell Res Ther. 2020; 11(1): 490. doi: 10.1186/s13287-020-02008-8

12. Jie X, Hu H, Nie B, Zhu L, Jiang H, Liu A. Effects of miR126 Expressing Adipose-Derived Stem Cells on Fat Graft Survival and Angiogenesis. Aesthetic Plast Surg. 2023; 47(2): 825-832. doi: 10.1007/s00266-022-03077-1

13. Li K, Luo R, Yu X, Dong W, Hao G, Hu D, et al. Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction. Clin Transl Med. 2025; 15(3): e70250. doi: 10.1002/ctm2.70250

14. Teufelsbauer M, Stickler S, Eggerstorfer MT, Hammond DC, Lang C, Hamilton G. Markers for the angiogenic potential of fat grafts. Wien Klin Wochenschr. 2025; 137(21-22): 684-692. doi: 10.1007/s00508-025-02532-8

15. Wang M, Wang C, Chen M, Xi Y, Cheng W, Mao C, et al. Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release. ACS Nano. 2019; 13(9): 10279–10293. doi: 10.1021/acsnano.9b03656

16. Bellini E, Grieco MP, Raposio E. The science behind autologous fat grafting. Ann Med Surg. 2017; 24: 65–73. doi: 10.1016/j.amsu.2017.11.001

17. Moustaki M, Papadopoulos O, Verikokos C, Karypidis D, Masud D, Kostakis A, et al. Application of adipose-derived stromal cells in fat grafting: Basic science and literature review. Exp Ther Med. 2017; 14(3): 2415-2423. doi: 10.3892/etm.2017.4811

18. Burlova MG, Kochneva IS, Vasilyev VS, Korableva NP, Evlakhova NA. Fat transfer breast augmentation: 12-year experience. Plastic Surgery and Aesthetic Medicine. 2024; (2): 28-37. (In Russ.). doi: 10.17116/plast.hirurgia202402128

19. Chang CS, Lanni MA, Mirzabeigi MN, Bucky LP. Large-Volume Fat Grafting: Identifying Risk Factors for Fat Necrosis. Plast Reconstr Surg. 2022; 150(5): 941e-949e. doi: 10.1097/PRS.0000000000009655

20. Gao S, Lu B, Zhou R, Gao W. Research progress of mechanisms of fat necrosis after autologous fat grafting: A review. Medicine (Baltimore). 2023; 102 (10): e33220. doi: 10.1097/MD.0000000000033220

21. Vasilyev VS, Burlova MG, Volchenko AA, Gurba MA, Vasilyev SA, Vasilyev IS. Fat grafting for breast shaping after implant removal. Plastic Surgery and Aesthetic Medicine. 2025; (2): 61-69. (In Russ.). doi: 10.17116/plast.hirurgia202502161

22. Kastyro IV, Ibadullaeva SS, Lavrentyeva EA, Ganshin IB, Khlystalov MV, Moroz SE, et al. Changes in the morphofunctional state of sebaceous glands in rats after fat autotransplantation in rats at late stages. Head and neck. Russian Journal. 2025; 13(2): 29–36. doi: 10.25792/HN.2025.13.2.29-36

23. Moroz SE, Lavrentieva EA, Khlystalov MV, Ibadullaeva SS, Popadyuk VI, Kastyro IV, et al. Pathomorphological changes in tissues with various methods of transplantation of adipose tissue (experimental study). Head and neck. Russian Journal. 2024; 12(4): 41–49. doi: 10.25792/HN.2024.12.4.41-49

24. Liu X, Yao Y, Zhu Y, Lu F, Chen X. Inhibition of Adipocyte Necroptosis Alleviates Fat Necrosis and Fibrosis After Grafting in a Murine Model. Aesthet Surg J. 2024; 44(8): NP585-NP605. doi: 10.1093/asj/sjae108

25. Khlystalov MV, Moroz SE, Kastyro IV, Lavrentieva EA, Ibadullaeva SS, Ganshin IB, et al. Angiogenesis in the autologous adipose tissue graft after various methods of preoperative fat treatment in rats. Head and neck. Russian Journal. 2024; 12(3): 57–62. doi: 10.25792/HN.2024.12.3.57-62

26. Burlova MG, Kochneva IS, Korableva NP, Evlakhova NA. Lipofilling for correction of various breast deformations. Plastic Surgery and Aesthetic Medicine. 2024; (1): 66-83. (In Russ.). doi: 10.17116/plast.hirurgia202401166

27. Burlova MG, Korableva NP, Gretskova EE. Correction of tubular breast using lipofilling. Plastic Surgery and Aesthetic Medicine. 2024; (3): 52-61. (In Russ.). doi: 10.17116/plast.hirurgia202403152

28. Rakhimov AYa, Fayzullin TR, Vasilyev VS, Sergeev IV. Lipofilling safety: mechanisms, prevention and treatment of severe complications of injectable adipose tissue transplantation. Plastic Surgery and Aesthetic Medicine. 2020; (4): 73-78. (In Russ.). doi: 10.17116/plast.hirurgia202004173

29. Jiang X, Cao H, He X, Zou X, Mao H, Tang L, et al. Skin necrosis after autologous fat grafting for augmentation rhinoplasty: a case report and review of the literature. J Cosmet Laser Ther. 2024; 26(5-8): 138-142. doi: 10.1080/14764172.2024.2421013

30. Bhoopalam M, Atayeva R, Tiongco RFP, Heron MJ, Girard AO, Er S, et al. Are We Speaking the Same Language? A Systematic Review on the Use of Consistent Language in Reporting Fat Necrosis in Autologous Fat Grafting of the Breast. Aesthetic Plast Surg. 2024; 48(7): 1403-1416. doi: 10.1007/s00266-023-03568-9

31. Wang X, Li Q, He S, Bai J, Ma C, Zhang L, et al. LncRNA FENDRR with m6A RNA methylation regulates hypoxia-induced pulmonary artery endothelial cell pyroptosis by mediating DRP1 DNA methylation. Mol Med. 2022; 28(1): 126. doi: 10.1186/s10020-022-00551-z

32. Liu Q, Song T, Chen B, Zhang J, Li W. Ferroptosis of brain microvascular endothelial cells contributes to hypoxia-induced blood-brain barrier injury. FASEB J. 2023; 37(5): e22874. doi: 10.1096/fj.202201765R

33. Jiang Y, Huang J, Xia Y, Sun Z, Hu P, Wang D, et al. Hypoxia activates GPR146 which participates in pulmonary vascular remodeling by promoting pyroptosis of pulmonary artery endothelial cells. Eur J Pharmacol. 2023; 941: 175502. doi: 10.1016/j.ejphar.2023.175502

34. Kazmirczak F, Vogel NT, Prisco SZ, Patterson MT, Annis J, Moon RT, et al. Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension. Circ Res. 2024; 135(11): 1067-1083. doi: 10.1161/CIRCRESAHA.123.324138

35. Thayaparan D, Emoto T, Khan AB, Besla R, Hamidzada H, El-Maklizi M, et al. Endothelial dysfunction drives atherosclerotic plaque macrophage-dependent abdominal aortic aneurysm formation. Nat Immunol. 2025; 26(5): 706-721. doi: 10.1038/s41590-025-02132-8

36. Zhang Z, Zhao L, Zhou X, Meng X, Zhou X. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Front Immunol. 2023; 13: 1098725. doi: 10.3389/fimmu.2022.1098725

37. Ivanov AY, Petrov AE, Vershinina EA, Galagudza MM, Vlasov TD. Evidence of active regulation of cerebral venous tone in individuals undergoing embolization of brain arteriovenous malformations. JApplPhysiol. 2013; 115(11): 1666-71. doi: 10.1152/japplphysiol.00951.2013