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Review Article

An appraisal of vascular endothelial growth factor (VEGF): the dynamic molecule of wound healing and its current clinical applications

, ORCID Icon, , , , & show all
Pages 73-88 | Received 26 Dec 2021, Accepted 03 May 2022, Published online: 18 May 2022

References

  • Adini, A., I. Adini, Z. L. Chi, R. Derda, A. E. Birsner, B. D. Matthews, and R. J. D'Amato. 2017. “A Novel Strategy to Enhance Angiogenesis in Vivo Using the Small VEGF-Binding Peptide PR1P.” Angiogenesis 20 (3): 399–408. doi:10.1007/s10456-017-9556-7.
  • An, Y., W. J. Liu, P. Xue, Y. Ma, L. Q. Zhang, B. Zhu, M. Qi, et al. 2018. “Autophagy Promotes MSC-Mediated Vascularization in Cutaneous Wound Healing via Regulation of VEGF Secretion.” Cell Death & Disease 9 (2): 58. doi:10.1038/s41419-017-0082-8.
  • Ancelin, M., S. Chollet-Martin, M. A. Hervé, C. Legrand, J. El Benna, and M. Perrot-Applanat. 2004. “Vascular Endothelial Growth Factor VEGF189 Induces Human Neutrophil Chemotaxis in Extravascular Tissue via an Autocrine Amplification Mechanism.” Laboratory Investigation; A Journal of Technical Methods and Pathology 84 (4): 502–512. doi:10.1038/labinvest.3700053.
  • Antonelli-Orlidge, A., K. B. Saunders, S. R. Smith, and P. A. D'Amore. 1989. “An Activated Form of Transforming Growth Factor Beta is Produced by Cocultures of Endothelial Cells and Pericytes.” Proceedings of the National Academy of Sciences of the United States of America 86 (12): 4544–4548. doi:10.1073/pnas.86.12.4544.
  • Avogaro, A., M. Albiero, L. Menegazzo, S. de Kreutzenberg, and G. P. Fadini. 2011. “Endothelial Dysfunction in Diabetes: The Role of Reparatory Mechanisms.” Diabetes Care 34 (Suppl 2): S285–S290. doi:10.2337/dc11-s239.
  • Bao, P., A. Kodra, M. Tomic-Canic, M. S. Golinko, H. P. Ehrlich, and H. Brem. 2009. “The Role of Vascular Endothelial Growth Factor in Wound Healing.” The Journal of Surgical Research 153 (2): 347–358. doi:10.1016/j.jss.2008.04.023.
  • Barcelos, Lucíola S., Cécile Duplaa, Nicolle Kränkel, Gallia Graiani, Gloria Invernici, Rajesh Katare, Mauro Siragusa, et al. 2009. “Human CD133+ Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling.” Circulation Research 104 (9): 1095–1102. doi:10.1161/CIRCRESAHA.108.192138.
  • Barleon, B., S. Hauser, C. Schöllmann, K. Weindel, D. Marmé, A. Yayon, H. A. Weich, et al. 1994. “Differential Expression of the Two VEGF Receptors Flt and KDR in Placenta and Vascular Endothelial Cells.” Journal of Cellular Biochemistry 54 (1): 56–66. doi:10.1002/jcb.240540107.
  • Barleon, B., S. Sozzani, D. Zhou, H. A. Weich, A. Mantovani, and D. Marmé. 1996. “Migration of Human Monocytes in Response to Vascular Endothelial Growth Factor (VEGF) is Mediated via the VEGF Receptor Flt-1.” Blood 87 (8): 3336–3343.
  • Basu, S., T. Ramchuran Panray, T. Bali  Singh, A. K. Gulati, and V. K. Shukla. 2009. “A Prospective, Descriptive Study to Identify the Microbiological Profile of Chronic  Wounds in Outpatients.” Ostomy Wound Manage 55 (1): 14–20.
  • Baumgartner, I., A. Pieczek, O. Manor, R. Blair, M. Kearney, K. Walsh, J. M. Isner, et al. 1998. “Constitutive Expression of phVEGF165 after Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients with Critical Limb Ischemia.” Circulation 97 (12): 1114–1123. doi:10.1161/01.cir.97.12.1114.
  • Bermont, L., F. Lamielle, S. Fauconnet, H. Esumi, A. Weisz, and G. L. Adessi. 2000. “Regulation of Vascular Endothelial Growth Factor Expression by Insulin-like Growth factor-I in Endometrial Adenocarcinoma Cells.” International Journal of Cancer 85 (1): 117–123. doi:10.1002/(SICI)1097-0215(20000101)85:1<117::AID-IJC21>3.0.CO;2-X.
  • Birkenhauer, E., and S. Neethirajan. 2015. “A Double-Edged Sword: The Role of VEGF in Wound Repair and Chemoattraction of Opportunist Pathogens.” International Journal of Molecular Sciences 16 (4): 7159–7172. doi:10.3390/ijms16047159.
  • Borenstein, Jeffrey T., Katie Megley, Kimberly Wall, Eleanor M. Pritchard, David. Truong, David L. Kaplan, Sarah L. Tao, et al. 2010. “Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs.” Materials 3 (3): 1833–1844. doi:10.3390/ma3031833.
  • Boyar, V. 2021. “Association of Systemic or Intravitreal Antivascular Endothelial Growth Factor (anti-VEGF) and Impaired Wound Healing in Pediatric Patients: Collagen to the Rescue.” Journal of Wound, Ostomy, and Continence Nursing: official Publication of the Wound, Ostomy and Continence Nurses Society 48 (3): 256–261. doi:10.1097/WON.0000000000000764.
  • Caballero, Sergio, Nilanjana Sengupta, Aqeela Afzal, Kyung-Hee Chang, Sergio Li Calzi, Dennis L. Guberski, Timothy S. Kern, et al. 2007. “Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells.” Diabetes 56 (4): 960–967. doi:10.2337/db06-1254.
  • Carmeliet, P. 2003. “Angiogenesis in Health and Disease.” Nature Medicine 9 (6): 653–660. doi:10.1038/nm0603-653.
  • Chu, Liang-Hui, Vijay Chaitanya Ganta, Min H. Choi, George Chen, Stacey D. Finley, Brian H. Annex, Aleksander S. Popel, et al. 2016. “A Multiscale Computational Model Predicts Distribution of anti-Angiogenic Isoform VEGF165b in Peripheral Arterial Disease in Human and Mouse.” Scientific Reports 6: 37030. doi:10.1038/srep37030.
  • Corral, C. J., A. Siddiqui, L. Wu, C. L. Farrell, D. Lyons, and T. A. Mustoe. 1999. “Vascular Endothelial Growth Factor is More Important than Basic Fibroblastic Growth Factor during Ischemic Wound Healing.” Archives of Surgery (Chicago, Ill: 1960) 134 (2): 200–205. doi:10.1001/archsurg.134.2.200.
  • Decaussin, Myriam, Hervé Sartelet, Catherine Robert, Denis Moro, Christine Claraz, Christian Brambilla, Elisabeth Brambilla, et al. 1999. “Expression of Vascular Endothelial Growth Factor (VEGF) and Its Two Receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in Non-Small Cell Lung Carcinomas (NSCLCs): Correlation with Angiogenesis and Survival.” The Journal of Pathology 188 (4): 369–377. doi:10.1002/(SICI)1096-9896(199908)188:4<369::AID-PATH381>3.0.CO;2-X.
  • Detmar, M., L. F. Brown, B. Berse, R. W. Jackman, B. M. Elicker, H. F. Dvorak, K. P. Claffey, et al. 1997. “Hypoxia Regulates the Expression of Vascular Permeability Factor/Vascular Endothelial Growth Factor (VPF/VEGF) and Its Receptors in Human Skin.” The Journal of Investigative Dermatology 108 (3): 263–268. doi:10.1111/1523-1747.ep12286453.
  • Dor, Yuval, Valentin Djonov, Rinat Abramovitch, Ahuva Itin, Glenn I. Fishman, Peter Carmeliet, Gadi Goelman, et al. 2002. “Conditional Switching of VEGF Provides New Insights into Adult Neovascularization and Pro-Angiogenic Therapy.” The EMBO Journal 21 (8): 1939–1947. doi:10.1093/emboj/21.8.1939.
  • Drinkwater, S. L., K. G. Burnand, R. Ding, and A. Smith. 2003. “Increased but Ineffectual Angiogenic Drive in Nonhealing Venous Leg Ulcers.” Journal of Vascular Surgery 38 (5): 1106–1112. doi:10.1016/S0741-5214(03)01053-X.
  • Dulmovits, B. M., and I. M. Herman. 2012. “Microvascular Remodeling and Wound Healing: A Role for Pericytes.” The International Journal of Biochemistry & Cell Biology 44 (11): 1800–1812. doi:10.1016/j.biocel.2012.06.031.
  • Eliceiri, B. P., and D. A. Cheresh. 1999. “The Role of Alphav Integrins during Angiogenesis: insights into Potential Mechanisms of Action and Clinical Development.” The Journal of Clinical Investigation 103 (9): 1227–1230. doi:10.1172/JCI6869.
  • Eming, Sabine A., Manuel Koch, Andreas Krieger, Bent Brachvogel, Sandra Kreft, Leena Bruckner-Tuderman, Thomas Krieg, et al. 2010. “Differential Proteomic Analysis Distinguishes Tissue Repair Biomarker Signatures in Wound Exudates Obtained from Normal Healing and Chronic Wounds.” Journal of Proteome Research 9 (9): 4758–4766. doi:10.1021/pr100456d.
  • Engerman, R. L., D. Pfaffenbach, and M. D. Davis. 1967. “Cell Turnover of Capillaries.” Laboratory Investigation; a Journal of Technical Methods and Pathology 17 (6): 738–743.
  • Enholm, B., T. Karpanen, M. Jeltsch, H. Kubo, F. Stenback, R. Prevo, D. G. Jackson, et al. 2001. “Adenoviral Expression of Vascular Endothelial Growth factor-C Induces Lymphangiogenesis in the Skin [Published Correction Appears in Circ Res 2001 Jul 6;89(1):E15].” Circulation Research 88 (6): 623–629. doi:10.1161/01.res.88.6.623.
  • Falanga, V. 2005. “Wound Healing and Its Impairment in the Diabetic Foot.” Lancet (London, England) 366 (9498): 1736–1743. doi:10.1016/S0140-6736(05)67700-8.
  • Ferrara, N. 2001. “Role of Vascular Endothelial Growth Factor in Regulation of Physiological Angiogenesis.” American Journal of Physiology. Cell Physiology 280 (6): C1358–C1366. doi:10.1152/ajpcell.2001.280.6.C1358.
  • Frank, S., G. Hübner, G. Breier, M. T. Longaker, D. G. Greenhalgh, and S. Werner. 1995. “Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes. Implications for Normal and Impaired Wound Healing.” The Journal of Biological Chemistry 270 (21): 12607–12613. doi:10.1074/jbc.270.21.12607.
  • Galiano, Robert D., Oren M. Tepper, Catherine R. Pelo, Kirit A. Bhatt, Matthew Callaghan, Nicholas Bastidas, Stuart Bunting, et al. 2004. “Topical Vascular Endothelial Growth Factor Accelerates Diabetic Wound Healing through Increased Angiogenesis and by Mobilizing and Recruiting Bone Marrow-Derived Cells.” The American Journal of Pathology 164 (6): 1935–1947. doi:10.1016/S0002-9440(10)63754-6.
  • Gendron, R. L., L. C. Adams, and H. Paradis. 2000. “Tubedown-1, a Novel Acetyltransferase Associated with Blood Vessel Development.” Developmental Dynamics 218 (2): 300–315. doi:10.1002/(SICI)1097-0177(200006)218:2<300::AID-DVDY5>3.0.CO;2-K.
  • Gohel, M. S., R. A. Windhaber, J. F. Tarlton, M. R. Whyman, and K. R. Poskitt. 2008. “The Relationship between Cytokine Concentrations and Wound Healing in Chronic Venous Ulceration.” Journal of Vascular Surgery 48 (5): 1272–1277. doi:10.1016/j.jvs.2008.06.042.
  • Goswami, A. G., S. Basu, and V. K. Shukla. 2021. “Wound Healing in the Golden Agers: what we Know and the Possible Way Ahead.” The International Journal of Lower Extremity Wounds 153473462110378. Epub ahead of print. doi:10.1177/15347346211037841.
  • Gounis, M. J., M.-G. Spiga, R. M. Graham, A. Wilson, S. Haliko, B. B. Lieber, A. K. Wakhloo, et al. 2005. “Angiogenesis is Confined to the Transient Period of VEGF Expression That Follows Adenoviral Gene Delivery to Ischemic Muscle.” Gene Therapy 12 (9): 762–771. doi:10.1038/sj.gt.3302481.
  • Greve, Joan M., Timothy J. Chico, Hope Goldman, Stuart Bunting, Franklin V. Peale, Ann Daugherty, Nicholas van Bruggen, et al. 2006. “Magnetic Resonance Angiography Reveals Therapeutic Enlargement of Collateral Vessels Induced by VEGF in a Murine Model of Peripheral Arterial Disease.” Journal of Magnetic Resonance Imaging 24 (5): 1124–1132. doi:10.1002/jmri.20731.
  • Gucciardo, L., R. Lories, N. Ochsenbein-Kölble, E. Done', A. Zwijsen, and J. Deprest. 2009. “Fetal Mesenchymal Stem Cells: isolation, Properties and Potential Use in Perinatology and Regenerative Medicine.” BJOG: An International Journal of Obstetrics and Gynaecology 116 (2): 166–172. doi:10.1111/j.1471-0528.2008.02005.x.
  • Guo, Jianming, Haidi Hu, Jolanta Gorecka, Hualong Bai, Hao He, Roland Assi, Toshihiko Isaji, et al. 2018. “Adipose-Derived Mesenchymal Stem Cells Accelerate Diabetic Wound Healing in a Similar Fashion as Bone Marrow-Derived Cells.” American Journal of Physiology-Cell Physiology 315 (6): C885–C896. doi:10.1152/ajpcell.00120.2018.
  • Gupta, R., J. Tongers, and D. W. Losordo. 2009. “Human Studies of Angiogenic Gene Therapy.” Circulation Research 105 (8): 724–736. doi:10.1161/CIRCRESAHA.109.200386.
  • Hadi, H. A., and J. A. Suwaidi. 2007. “Endothelial Dysfunction in Diabetes Mellitus.” Vascular Health and Risk Management 3 (6): 853–876.
  • Hanahan, D., and J. Folkman. 1996. “Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis.” Cell 86 (3): 353–364. doi:10.1016/s0092-8674(00)80108-7.
  • Hanft, J. R., R. A. Pollak, A. Barbul, C. van Gils, P. S. Kwon, S. M. Gray, C. J. Lynch, et al. 2008. “Phase I Trial on the Safety of Topical rhVEGF on Chronic Neuropathic Diabetic Foot Ulcers.” Journal of Wound Care 17 (1): 30–37. doi:10.12968/jowc.2008.17.1.27917.
  • Hashimoto, E., K. Kage, T. Ogita, T. Nakaoka, R. Matsuoka, and Y. Kira. 1994. “Adenosine as an Endogenous Mediator of Hypoxia for Induction of Vascular Endothelial Growth Factor mRNA in U-937 Cells.” Biochemical and Biophysical Research Communications 204 (1): 318–324. doi:10.1006/bbrc.1994.2462.
  • Herouy, Y., S. Kreis, T. Mueller, T. Duerk, G. Martiny-Baron, P. Reusch, F. May, et al. 2009. “Inhibition of Angiogenesis in Lipodermatosclerosis: Implication for Venous Ulcer Formation.” International Journal of Molecular Medicine. 24 (5): 645–651. doi:10.3892/ijmm_00000275.
  • Hoeben, A., B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn. 2004. “Vascular Endothelial Growth Factor and Angiogenesis.” Pharmacological Reviews 56 (4): 549–580. doi:10.1124/pr.56.4.3.
  • Houck, K. A., D. W. Leung, A. M. Rowland, J. Winer, and N. Ferrara. 1992. “Dual Regulation of Vascular Endothelial Growth Factor Bioavailability by Genetic and Proteolytic Mechanisms.” The Journal of Biological Chemistry 267 (36): 26031–26037.
  • Howdieshell, T. R., D. Callaway, W. L. Webb, M. D. Gaines, C. D. Procter Jr, Sathyanarayana  , J. S. Pollock, et al. 2001. “Antibody Neutralization of Vascular Endothelial Growth Factor Inhibits Wound Granulation Tissue Formation.” The Journal of Surgical Research 96 (2): 173–182. doi:10.1006/jsre.2001.6089.
  • Isner, J. M., I. Baumgartner, G. Rauh, R. Schainfeld, R. Blair, O. Manor, S. Razvi, et al. 1998. “Treatment of Thromboangiitis Obliterans (Buerger's Disease) by Intramuscular Gene Transfer of Vascular Endothelial Growth Factor: preliminary Clinical Results.” Journal of Vascular Surgery 28 (6): 964–975. doi:10.1016/S0741-5214(98)70022-9.
  • Jacobi, Johannes, Betty Y. Y. Tam, Uma Sundram, Georges von Degenfeld, Helen M. Blau, Calvin J. Kuo, John P. Cooke, et al. 2004. “Discordant Effects of a Soluble VEGF Receptor on Wound Healing and Angiogenesis.” Gene Therapy 11 (3): 302–309. doi:10.1038/sj.gt.3302162.
  • Powerski Maciej Janusz, D. Henrich, D. Wastl, A. Sander, and I. Marzi. 2010. “Surgical Wound Fluid from Elderly Patients Shows a Dramatically Reduced Potential to Stimulate in-Vitro Recruitment and Differentiation of Endothelial Progenitor Cells: role of VEGF-165 and TGF-β1.” Wounds 22 (8): 204–211.
  • Ji, J. W., F. Mac Gabhann, and A. S. Popel. 2007. “Skeletal Muscle VEGF Gradients in Peripheral Arterial Disease: simulations of Rest and Exercise.” American Journal of Physiology. Heart and Circulatory Physiology 293 (6): H3740–H3749. doi:10.1152/ajpheart.00009.2007.
  • Jünger, M., A. Steins, M. Hahn, and H. M. Häfner. 2000. “Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI).” Microcirculation 7 (S1): S3–S12. doi:10.1080/713774003.
  • Kajdaniuk, D., B. Marek, H. Borgiel-Marek, and B. Kos-Kudła. 2011. “Vascular Endothelial Growth Factor (VEGF) - Part 1: In Physiology and Pathophysiology.” Endokrynologia Polska 62 (5): 444–455.
  • Karlsson, T., B. C. Lagerholm, E. Vikström, V. M. Loitto, and K. E. Magnusson. 2013. “Water Fluxes through Aquaporin-9 Prime Epithelial Cells for Rapid Wound Healing.” Biochemical and Biophysical Research Communications 430 (3): 993–998. doi:10.1016/j.bbrc.2012.11.125.
  • Kevil, C. G., D. K. Payne, E. Mire, and J. S. Alexander. 1998. “Vascular Permeability Factor/Vascular Endothelial Cell Growth Factor-Mediated Permeability Occurs through Disorganization of Endothelial Junctional Proteins.” The Journal of Biological Chemistry 273 (24): 15099–15103. doi:10.1074/jbc.273.24.15099.
  • Kohn, S., J. A. Nagy, H. F. Dvorak, and A. M. Dvorak. 1992. “Pathways of Macromolecular Tracer Transport across Venules and Small Veins. Structural Basis for the Hyperpermeability of Tumor Blood Vessels.” Laboratory Investigation 67 (5): 596–607.
  • Kolano, Paweł, Igor Bednarski, Aleksandra Lesiak, Małgorzata Skibińska, Olga Stasikowska-Kanicka, Marian Danilewicz, Joanna Narbutt, et al. 2020. “Overexpression of Cathepsin K and Vascular Endothelial Growth Factor in Chronic Venous Ulcerations.” Advances in Dermatology and Allergology 37 (2): 234–239. doi:10.5114/ada.2020.94840.
  • Kusumanto, Y. H., V. van Weel, N. H. Mulder, A. J. Smit, J. J. A. M. van den Dungen, J. M. M. Hooymans, W. J. Sluiter, et al. 2006. “Treatment with Intramuscular Vascular Endothelial Growth Factor Gene Compared with Placebo for Patients with Diabetes Mellitus and Critical Limb Ischemia: A Double-Blind Randomized Trial.” Human Gene Therapy 17 (6): 683–691. doi:10.1089/hum.2006.17.683.
  • Kutcher, M. E., A. Y. Kolyada, H. K. Surks, and I. M. Herman. 2007. “Pericyte Rho GTPase Mediates Both Pericyte Contractile Phenotype and Capillary Endothelial Growth State.” The American Journal of Pathology 171 (2): 693–701. doi:10.2353/ajpath.2007.070102.
  • Lähteenvuo, J., and A. Rosenzweig. 2012. “Effects of Aging on Angiogenesis.” Circulation Research 110 (9): 1252–1264. doi:10.1161/CIRCRESAHA.111.246116.
  • Lauer, G., S. Sollberg, M. Cole, I. Flamme, J. Stürzebecher, K. Mann, T. Krieg, et al. 2000. “Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds.” The Journal of Investigative Dermatology 115 (1): 12–18. doi:10.1046/j.1523-1747.2000.00036.x.
  • Lee, S., A. Zeiger, J. M. Maloney, M. Kotecki, K. J. Van Vliet, and I. M. Herman. 2010. “Pericyte Actomyosin-Mediated Contraction at the Cell-Material Interface Can Modulate the Microvascular Niche.” Journal of Physics. Condensed Matter: An Institute of Physics Journal 22 (19): 194115. doi:10.1088/0953-8984/22/19/194115.
  • Leibovich, S. J., P. J. Polverini, H. M. Shepard, D. M. Wiseman, V. Shively, and N. Nuseir. 1987. “Macrophage-Induced Angiogenesis is Mediated by Tumour Necrosis Factor-Alpha.” Nature 329 (6140): 630–632. doi:10.1038/329630a0.
  • Leung, D. W., G. Cachianes, W. J. Kuang, D. V. Goeddel, and N. Ferrara. 1989. “Vascular Endothelial Growth Factor is a Secreted Angiogenic Mitogen.” Science (New York, N.Y.) 246 (4935): 1306–1309. doi:10.1126/science.2479986.
  • Loomans, Cindy Jm, Rien van Haperen, Jacques M. Duijs, Caroline Verseyden, Rini de Crom, Pieter Jm Leenen, Hemmo A. Drexhage, et al. 2009. “Differentiation of Bone Marrow-Derived Endothelial Progenitor Cells is Shifted into a Proinflammatory Phenotype by Hyperglycemia.” Molecular Medicine (Cambridge, Mass.) 15 (5-6): 152–159. doi:10.2119/molmed.2009.00032.
  • Lord, Megan S., April L. Ellis, Brooke L. Farrugia, John M. Whitelock, Hernan Grenett, Chuanyu Li, Robert L. O'Grady, et al. 2017. “Perlecan and Vascular Endothelial Growth Factor-Encoding DNA-Loaded Chitosan Scaffolds Promote Angiogenesis and Wound Healing.” Journal of Controlled Release: official Journal of the Controlled Release Society 250: 48–61. doi:10.1016/j.jconrel.2017.02.009.
  • Losi, P., E. Briganti, C. Errico, A. Lisella, E. Sanguinetti, F. Chiellini, and G. Soldani. 2013. “Fibrin-Based Scaffold Incorporating VEGF- and bFGF-Loaded Nanoparticles Stimulates Wound Healing in Diabetic Mice.” Acta Biomaterialia 9 (8): 7814–7821. doi:10.1016/j.actbio.2013.04.019.
  • Maisonpierre, P. C., C. Suri, P. F. Jones, S. Bartunkova, S. J. Wiegand, C. Radziejewski, D. Compton, et al. 1997. “Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in Vivo Angiogenesis.” Science (New York, N.Y.) 277 (5322): 55–60. doi:10.1126/science.277.5322.55.
  • Mäkinen, Kimmo, Hannu Manninen, Marja Hedman, Pekka Matsi, Hanna Mussalo, Esko Alhava, Seppo Ylä-Herttuala, et al. 2002. “Increased Vascularity Detected by Digital Subtraction Angiography after VEGF Gene Transfer to Human Lower Limb Artery: A Randomized, Placebo-Controlled, Double-Blinded Phase II Study.” Molecular Therapy: The Journal of the American Society of Gene Therapy 6 (1): 127–133. doi:10.1006/mthe.2002.0638.
  • Möhle, R., D. Green, M. A. Moore, R. L. Nachman, and S. Rafii. 1997. “Constitutive Production and Thrombin-Induced Release of Vascular Endothelial Growth Factor by Human Megakaryocytes and Platelets.” Proceedings of the National Academy of Sciences of the United States of America 94 (2): 663–668. doi:10.1073/pnas.94.2.663.
  • Morbidelli, L., C. H. Chang, J. G. Douglas, H. J. Granger, F. Ledda, and M. Ziche. 1996. “Nitric Oxide Mediates Mitogenic Effect of VEGF on Coronary Venular Endothelium.” The American Journal of Physiology 270 (1 Pt 2): H411–H415. doi:10.1152/ajpheart.1996.270.1.H411.
  • Murohara, T., J. R. Horowitz, M. Silver, Y. Tsurumi, D. Chen, A. Sullivan, J. M. Isner, et al. 1998. “Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability via Nitric Oxide and Prostacyclin.” Circulation 97 (1): 99–107. doi:10.1161/01.cir.97.1.99.
  • Murphy, M. A., W. P. Joyce, C. Condron, and D. Bouchier-Hayes. 2002. “A Reduction in Serum Cytokine Levels Parallels Healing of Venous Ulcers in Patients Undergoing Compression Therapy.” European Journal of Vascular and Endovascular Surgery: The Official Journal of the European Society for Vascular Surgery 23 (4): 349–352. doi:10.1053/ejvs.2002.1597.
  • Ninikoski, J., C. Heughan, and T. K. Hunt. 1971. “Oxygen and Carbon Dioxide Tensions in Experimental Wounds.” Surgery, Gynecology & Obstetrics 133 (6): 1003–1007.
  • Nosrati, H., R. Aramideh Khouy, A. Nosrati, M. Khodaei, M. Banitalebi-Dehkordi, K. Ashrafi-Dehkordi, S. Sanami, and Z. Alizadeh. 2021. “Nanocomposite Scaffolds for Accelerating Chronic Wound Healing by Enhancing Angiogenesis.” Journal of Nanobiotechnology 19 (1): 1. doi:10.1186/s12951-020-00755-7.
  • Olofsson, B., E. Korpelainen, M. S. Pepper, S. J. Mandriota, K. Aase, V. Kumar, Y. Gunji, et al. 1998. “Vascular Endothelial Growth Factor B (VEGF-B) Binds to VEGF Receptor-1 and Regulates Plasminogen Activator Activity in Endothelial Cells.” Proceedings of the National Academy of Sciences of the United States of America 95 (20): 11709–11714. doi:10.1073/pnas.95.20.11709.
  • Pepper, M. S., N. Ferrara, L. Orci, and R. Montesano. 1991. “Vascular Endothelial Growth Factor (VEGF) Induces Plasminogen Activators and Plasminogen Activator Inhibitor-1 in Microvascular Endothelial Cells.” Biochemical and Biophysical Research Communications 181 (2): 902–906. doi:10.1016/0006-291x(91)91276-i.
  • Peschen, M., H. Grenz, B. Brand-Saberi, M. Bunaes, J. C. Simon, E. Schöpf, W. Vanscheidt, et al. 1998. “Increased Expression of Platelet-Derived Growth Factor Receptor Alpha and Beta and Vascular Endothelial Growth Factor in the Skin of Patients with Chronic Venous Insufficiency.” Archives of Dermatological Research 290 (6): 291–297. doi:10.1007/s004030050307.
  • Plouët, J., F. Moro, S. Bertagnolli, N. Coldeboeuf, H. Mazarguil, S. Clamens, F. Bayard, et al. 1997. “Extracellular Cleavage of the Vascular Endothelial Growth Factor 189-Amino Acid Form by Urokinase is Required for Its Mitogenic Effect.” The Journal of Biological Chemistry 272 (20): 13390–13396. doi:10.1074/jbc.272.20.13390.
  • Prior, B. M., H. T. Yang, and R. L. Terjung. 2004. “What Makes Vessels Grow with Exercise Training?” Journal of Applied Physiology (Bethesda, MD: 1985) 97 (3): 1119–1128. doi:10.1152/japplphysiol.00035.2004.
  • Pufe, T., F. Paulsen, W. Petersen, R. Mentlein, and M. Tsokos. 2003. “The Angiogenic Peptide Vascular Endothelial Growth Factor (VEGF) is Expressed in Chronic Sacral Pressure Ulcers.” The Journal of Pathology 200 (1): 130–136. doi:10.1002/path.1290.
  • Pugh, C. W., and P. J. Ratcliffe. 2003. “Regulation of Angiogenesis by Hypoxia: role of the HIF System.” Nature Medicine 9 (6): 677–684. doi:10.1038/nm0603-677.
  • Rajagopalan, S., M. Shah, A. Luciano, R. Crystal, and E. G. Nabel. 2001. “Adenovirus-Mediated Gene Transfer of VEGF (121) Improves Lower-Extremity Endothelial Function and Flow Reserve.” Circulation 104 (7): 753–755. doi:10.1161/hc3201.095192.
  • Rajagopalan, Sanjay, Emile R. Mohler, Robert J. Lederman, Farrell O. Mendelsohn, Jorge F. Saucedo, Corey K. Goldman, John Blebea, et al. 2003. “Regional Angiogenesis with Vascular Endothelial Growth Factor in Peripheral Arterial Disease: A Phase II Randomized, Double-Blind, Controlled Study of Adenoviral Delivery of Vascular Endothelial Growth Factor 121 in Patients with Disabling Intermittent Claudication.” Circulation 108 (16): 1933–1938. doi:10.1161/01.CIR.0000093398.16124.29.
  • Rivard, Alain, Marcy Silver, Dongfen Chen, Marianne Kearney, Meredith Magner, Brian Annex, Kevin Peters, et al. 1999. “Rescue of Diabetes-Related Impairment of Angiogenesis by Intramuscular Gene Therapy with adeno-VEGF.” American Journal of Pathology. 154 (2): 355–363. doi:10.1016/S0002-9440(10)65282-0.
  • Robson, M. C., D. P. Hill, P. D. Smith, X. Wang, K. Meyer-Siegler, F. Ko, J. S. VandeBerg, et al. 2000. “Sequential Cytokine Therapy for Pressure Ulcers: clinical and Mechanistic Response.” Annals of Surgery 231 (4): 600–611. doi:10.1097/00000658-200004000-00020.
  • Robson, M. C., L. G. Phillips, W. T. Lawrence, J. B. Bishop, J. S. Youngerman, P. G. Hayward, L. D. Broemeling, J. P. Heggers. 1992. “The Safety and Effect of Topically Applied Recombinant Basic Fibroblast Growth Factor on the Healing of Chronic Pressure Sores.” Ann Surg 216 (4): 401–408.
  • Roman, Christopher D., Hak Choy, Lillian Nanney, Colin Riordan, Kelly Parman, David Johnson, R. Daniel Beauchamp, et al. 2002. “Vascular Endothelial Growth Factor-Mediated Angiogenesis Inhibition and Postoperative Wound Healing in Rats.” Journal of Surgical Research 105 (1): 43–47. doi:10.1006/jsre.2002.6444.
  • Sawano, A., S. Iwai, Y. Sakurai, M. Ito, K. Shitara, T. Nakahata, M. Shibuya, et al. 2001. “Flt-1, Vascular Endothelial Growth Factor Receptor 1, is a Novel Cell Surface Marker for the Lineage of Monocyte-Macrophages in Humans.” Blood 97 (3): 785–791. doi:10.1182/blood.v97.3.785.
  • Senger, D. R., S. J. Galli, A. M. Dvorak, C. A. Perruzzi, V. S. Harvey, and H. F. Dvorak. 1983. “Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid.” Science (New York, N.Y.) 219 (4587): 983–985. doi:10.1126/science.6823562.
  • Shibuya, M. 2001. “Structure and Function of VEGF/VEGF-Receptor System Involved in Angiogenesis.” Cell Structure and Function 26 (1): 25–35. doi:10.1247/csf.26.25.
  • Shoab, S. S., J. H. Scurr, and P. D. Coleridge-Smith. 1998. “Increased Plasma Vascular Endothelial Growth Factor among Patients with Chronic Venous Disease.” Journal of Vascular Surgery 28 (3): 535–540. doi:10.1016/S0741-5214(98)70141-7.
  • Shukla, V. K., Dinesh Shukla, Abhisek Singh, A. K. Tripathi, Sushil Jaiswal, and Somprakas Basu. 2008. “Risk Assessment for Pressure Ulcer: A Hospital-Based Study.” Journal of Wound, Ostomy, and Continence Nursing: official Publication of the Wound, Ostomy and Continence Nurses Society 35 (4): 407–411. doi:10.1097/01.WON.0000326661.24766.93.
  • Soker, S., S. Takashima, H. Q. Miao, G. Neufeld, and M. Klagsbrun. 1998. “Neuropilin-1 is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor.” Cell 92 (6): 735–745. doi:10.1016/S0092-8674(00)81402-6.
  • Spyridopoulos, I., E. Brogi, M. Kearney, A. B. Sullivan, C. Cetrulo, J. M. Isner, D. W. Losordo, et al. 1997. “Vascular Endothelial Growth Factor Inhibits Endothelial Cell Apoptosis Induced by Tumor Necrosis Factor-Alpha: balance between Growth and Death Signals.” Journal of Molecular and Cellular Cardiology 29 (5): 1321–1330. doi:10.1006/jmcc.1996.0365.
  • Stavri, G. T., I. C. Zachary, P. A. Baskerville, J. F. Martin, and J. D. Erusalimsky. 1995. “Basic Fibroblast Growth Factor Upregulates the Expression of Vascular Endothelial Growth Factor in Vascular Smooth Muscle Cells. Synergistic Interaction with Hypoxia.” Circulation 92 (1): 11–14. doi:10.1161/01.cir.92.1.11.
  • Stojadinovic, O. K. A., M. Golinko, M. Tomic-Canic, and H. Brem. 2007. “A Novel, Non-Angiogenic Mechanism of VEGF: stimulation of Keratinocyte and Fibroblast Migration.” Wound Repair and Regeneration A30.
  • Sun, Naidi, Bo Ning, Kenny M. Hansson, Anthony C. Bruce, Scott A. Seaman, Chenchu Zhang, Michaela Rikard, et al. 2018. “Modified VEGF-A mRNA Induces Sustained Multifaceted Microvascular Response and Accelerates Diabetic Wound Healing.” Scientific Reports 8 (1): 17509. doi:10.1038/s41598-018-35570-6.
  • Suri, C., J. McClain, G. Thurston, D. M. McDonald, H. Zhou, E. H. Oldmixon, T. N. Sato, et al. 1998. “Increased Vascularization in Mice Overexpressing Angiopoietin-1.” Science (New York, N.Y.) 282 (5388): 468–471. doi:10.1126/science.282.5388.468.
  • Thurston, G., J. S. Rudge, E. Ioffe, H. Zhou, L. Ross, S. D. Croll, N. Glazer, et al. 2000. “Angiopoietin-1 Protects the Adult Vasculature against Plasma Leakage.” Nature Medicine 6 (4): 460–463. doi:10.1038/74725.
  • Tsou, R., C. Fathke, L. Wilson, K. Wallace, N. Gibran, and F. Isik. 2002. “Retroviral Delivery of Dominant-Negative Vascular Endothelial Growth Factor Receptor Type 2 to Murine Wounds Inhibits Wound Angiogenesis.” Wound Repair and Regeneration: official Publication of the Wound Healing Society [and] the European Tissue Repair Society 10 (4): 222–229. doi:10.1046/j.1524-475x.2002.10405.x.
  • Unemori, E. N., N. Ferrara, E. A. Bauer, and E. P. Amento. 1992. “Vascular Endothelial Growth Factor Induces Interstitial Collagenase Expression in Human Endothelial Cells.” Journal of Cellular Physiology 153 (3): 557–562. doi:10.1002/jcp.1041530317.
  • Vinci, M. C., B. Visentin, F. Cusinato, G. B. Nardelli, L. Trevisi, and S. Luciani. 2004. “Effect of Vascular Endothelial Growth Factor and Epidermal Growth Factor on Iatrogenic Apoptosis in Human Endothelial Cells.” Biochemical Pharmacology 67 (2): 277–284. doi:10.1016/j.bcp.2003.09.007.
  • Waltenberger, J., L. Claesson-Welsh, A. Siegbahn, M. Shibuya, and C. H. Heldin. 1994. “Different Signal Transduction Properties of KDR and Flt1, Two Receptors for Vascular Endothelial Growth Factor.” The Journal of Biological Chemistry 269 (43): 26988–26995. doi:10.1016/S0021-9258(18)47116-5.
  • Wang, C. G., Y. T. Lou, M. J. Tong, L. L. Zhang, Z. J. Zhang, Y. Z. Feng, S. Li, H. Z. Xu, and C. Mao. 2018. “Asperosaponin VI Promotes Angiogenesis and Accelerates Wound Healing in Rats via up-Regulating HIF-1α/VEGF Signaling.” Acta Pharmacologica Sinica 39 (3): 393–404. doi:10.1038/aps.2017.161.
  • Wang, Y., L. Wang, Z. Wen, J. Wang, Y. Zhu, H. Chen, H. Li, et al. 2018. “High IL-6 and VEGF-A Levels Correlate with Delayed Wound Healing in Cervical Lymph Node Tuberculosis Patients.” The International Journal of Tuberculosis and Lung Disease 22 (10): 1227–1232. doi:10.5588/ijtld.18.0027.
  • Watanabe, Y., and H. F. Dvorak. 1997. “Vascular Permeability Factor/Vascular Endothelial Growth Factor Inhibits Anchorage-Disruption-Induced Apoptosis in Microvessel Endothelial Cells by Inducing Scaffold Formation.” Experimental Cell Research 233 (2): 340–349. doi:10.1006/excr.1997.3583.
  • Wilgus, Traci A., Annette M. Matthies, Katherine A. Radek, Julia V. Dovi, Aime L. Burns, Ravi Shankar, Luisa A. DiPietro, et al. 2005. “Novel Function for Vascular Endothelial Growth Factor Receptor-1 on Epidermal Keratinocytes.” The American Journal of Pathology 167 (5): 1257–1266. doi:10.1016/S0002-9440(10)61213-8.
  • Wise, L. M., M. K. Inder, N. C. Real, G. S. Stuart, S. B. Fleming, and A. A. Mercer. 2012. “The Vascular Endothelial Growth Factor (VEGF)-E Encoded by Orf Virus Regulates Keratinocyte Proliferation and Migration and Promotes Epidermal Regeneration.” Cellular Microbiology 14 (9): 1376–1390. doi:10.1111/j.1462-5822.2012.01802.x.
  • Wu, F. T., M. O. Stefanini, F. Mac Gabhann, C. D. Kontos, B. H. Annex, and A. S. Popel. 2010. “VEGF and Soluble VEGF Receptor-1 (sFlt-1) Distributions in Peripheral Arterial Disease: An in Silico Model.” American Journal of Physiology. Heart and Circulatory Physiology 298 (6): H2174–H2191. doi:10.1152/ajpheart.00365.2009.
  • Yang, J. J., X. L. Wang, B. W. Shi, and F. Huang. 2013. “The Angiogenic Peptide Vascular Endothelial Growth Factor-Basic Fibroblast Growth Factor Signaling is up-Regulated in a Rat Pressure Ulcer Model.” Anatomical Record (Hoboken, NJ: 2007) 296 (8): 1161–1168. doi:10.1002/ar.22676.
  • Yebra, M., G. C. Parry, S. Strömblad, N. Mackman, S. Rosenberg, B. M. Mueller, D. A. Cheresh, et al. 1996. “Requirement of Receptor-Bound Urokinase-Type Plasminogen Activator for Integrin alphavbeta5-Directed Cell Migration.” The Journal of Biological Chemistry 271 (46): 29393–29399. doi:10.1074/jbc.271.46.29393.
  • Zakareia, F. A. 2012. “Correlation of Peripheral Arterial Blood Flow with Plasma Chemerin and VEGF in Diabetic Peripheral Vascular Disease.” Biomarkers in Medicine 6 (1): 81–87. doi:10.2217/bmm.11.85.
  • Zhang, E. Y., B. Gao, H. L. Shi, L. F. Huang, L. Yang, X. J. Wu, and Z. T. Wang. 2017. “20(S)-Protopanaxadiol Enhances Angiogenesis via HIF-1α-Mediated VEGF Secretion by Activating p70S6 Kinase and Benefits Wound Healing in Genetically Diabetic Mice.” Experimental & Molecular Medicine 49 (10): e387. doi:10.1038/emm.2017.151.
  • Zhu, Y., Y. Wang, Y. Jia, J. Xu, and Y. Chai. 2019. “Roxadustat Promotes Angiogenesis through HIF-1α/VEGF/VEGFR2 Signaling and Accelerates Cutaneous Wound Healing in Diabetic Rats.” Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society 27 (4): 324–334. doi:10.1111/wrr.12708.

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