VEGF: structure, biological activities, regulations and roles in the healing of diabetic ulcers
DOI:
https://doi.org/10.18203/2320-6012.ijrms20182801Keywords:
Diabetic ulcers, Regulations, Roles, Structure, VEGFAbstract
Diabetic ulcer patients can be hampered their ulcer healing process. The condition is caused by hyperglycemia and accumulation of advanced glycation end-products (AGEs) that can cause interference with VEGF and its receptors and signaling pathways. The VEGF core region is formed by a cystine bond motif with 8 invariant cystine residues in inter and intramolecular disulfide bound to the end of the central 4-stranded at each monomer with a side-by-side antiparallel orientation. VEGF stimulates angiogenesis in three dimensions, causing the encounter of microvascular endothelial cells, penetration into collagen gels and forming capillary-like structures. Regulation of VEGF gene expression through: (1) hypoxia; (2) cytokines and (3) differentiation and transformation. VEGF stimulates wound healing through several mechanisms such as collagen deposition, angiogenesis and epithelialisation.
References
Greer N, Foman NA, MacDonald R, Dorrian J, Fitzgerald P, Rutks I, et al. Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review. Ann Intern Med. 2013;159:532-42.
Moura LI, Dias AM, Carvalho E, De Sousa HC. Recent advances on the development of wound dressings for diabetic foot ulcer treatment: A review. Acta Biomater. 2013;9:7093-114.
Baquerizo Nole KL, Kirsner RS. Advanced wound care therapies in non-healing lower extremity ulcers: high expectations, low evidence. Evid Based Med. 2014;19:91.
Olczyk P, Mencner L, Komosinska-Vassev K. The role of extracellular matrix components in cutaneous wound healing. BioMed Res Int. 2014.
Demidova-Rice TN, Durham JT and Herman IM. Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing. Adv Wound Care. 2012;1:17.
Jung M, Lord MS, Cheng B, Lyons JG, Alkhouri H, Hughes JM, et al. Mast cells produce novel shorter forms of perlecan that contain functional endorepellin: a role in angiogenesis and wound healing. J Biol Chem. 2012;12:1.
Slusarz R, Gadomska G, Biercewicz M, Grzelak L, Szewczyk MT, Ros´c´ D, et al. The influence of selected demographic factors and wound location on the concentration of vascular endothelial growth factor (VEGF-A) in the wound healing process after neurosurgery: brief report. Wound Repair Regen. 2012;20:667.
Bai H, Forrester JV, and Zhao M. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors. Cytokine. 2012;55:110.
Drela E, Kulwas A, Jundziłł W, Góralczyk B, Boinska J, Drewniak W, et al. VEGF-A and PDGF-BB-angiogenic factors and the stage of diabetic foot syndrome advancement. Endokrynologia Polska. 2014;65(4):306-12.
Bates DO, Harper SJ. Regulation of vascular permeability by vascular endothelial growth factors. Vascul Pharmacol. 2003;39:225.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549.
Peplow PV, Baxter D. Gene expression and release of growth factors during delayed wound healing: a review of studies in diabetic animals and possible combined laser phototherapy and growth factor treatment to enhance healing. Photomed Laser Surg. 2012;30:617.
Stroncek JD, Reichert WM. Overview of wound healing in different tissue types. In Indwelling Neural Implants: Strategies for Contending with the in Vivo Environment, 1st ed.; Reichert, WM Ed.; CRC Press: Boca Raton, FL, USA. 2008
Simons M. Angiogenesis, arteriogenesis, and diabetes: paradigm reassessed?. J Am Coll Cardiology. 2005;46(5):835-7.
Pendsey SP. Understanding diabetic foot. Int J Diab Dev Ctries. 2010;30:75-79.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549-80.
Ferroni P, Roselli M, Guadagni F, Martini F, Mariotti S, Marchitelli E, et al. Biological effects of a software-controlled voltage pulse generator (Phy-Back PBK-2C) on the release of vascular endothelial growth factor (VEGF). In Vivo. 2005;19:949.
Brem H, Kodra A, Golinko MS, Entero H, Stojadinovic O, Wang VM, et al. Mechanism of sustained release of vascular growth factor in accelerating experimental diabetic healing. J Investigative Dermatol. 2009;129:2275-87.
Pandey AN. Role of anti-vascular endothelial growth factor (VEGF) in ophthalmology. Int J Basic Clin Pharmacol. 2013;2:683-8.
Ferrara N, Davis-Smyth T. The Biology of Vascular Endothelial Growth Factor. Endocrine Review. 1997;18:4-25.
Gerber HP, Condorelli F, Park J, Ferrara N. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem. 1997:272:23659-67.
Oltmanns KM, Gehring H, Rudolf S, Schultes B, Hackenberg C, Schweiger U, et al. Acute hypoxia decreases plasma VEGF concentration in healthy humans. Am J Physiol Endocrinol Metab. 2006;290(3):E434-9.
Harmey JH, Bouchier-Hayes D. Vascular endothelial growth factor (VEGF), a survival factor for tumour cells: implications for anti-angiogenic therapy. Bioessays. 2002;24:280-3.
Freedman SB, dan Isner JM. Therapeutic angiogenesis for coronary artery disease. Ann Intern Med. 2002;136:54-71.
Meyer KC, Cardoni A, Xiang ZZ. Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J Lab Clin Med. 2000;135:332-8.
Koyama S, Sato E, Haniuda M, Numanami H, Nagai S, Izumi T. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med. 2002;166:382-5.
Santos S, Peinado VI, Ramirez J, Morales-Blanhir J, Bastos R, Roca J, Rodriguez-Roisin R, Barbera JA. Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:1250-6.
Belgore FM, Blann AD, Li-Saw-Hee FL, Beevers DG, Lip GY. Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension. Am J Cardiol. 2001;87:805-7.
Chou E, Suzuma I, Way KJ, Opland D, Clermont AC, Naruse K, et al. Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue. Circulation. 2002;105:373-9.
Maeda T, Kawane T, Horiuchi N. Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology. 2003;144:681-92.
Walter R, Maggiorini M, Scherrer U, Contesse J, Reinhart WH. Effects of high-altitude exposure on vascular endothelial growth factor levels in man. Eur J Appl Physiol. 2001;85:113-7.
Maloney J, Wang D, Duncan T, Voelkel N, Ruoss S. Plasma vascular endothelial growth factor in acute mountain sickness. Chest. 2000;118:47-52.
Gunga HC, Kirsch K, Rocker L, Behn C, Koralewski E, Davila EH, et al. Vascular endothelial growth factor in exercising humans under different environmental conditions. Eur J Appl Physiol Occup Physiol. 1999;79:484-90.
Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes: implication for normal and impaired wound healing. J Biological Chemistry. 1995;270:12607-13.
Lerman OZ, Galiano RD, Armour M, Jamie P, Levine JP, Gurtner GC. Cellular dysfunction in the diabetic fibroblast impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am J Pathol. 2003;162:303-12.
Velazquez OC. Angiogenesis and vasculogenesis: Inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing. J Vasc Surg. 2007;45:39A-47A.
Waltenberger J. New horizons in diabetes therapy: the angiogenesis paradox in diabetes: description of problem and presentation of unifying hypothesis. Immun Endo Metab Agents in Med Chem. 2007;7:87-93.
Ryu JK. Therapeutic Angiogenesis: The Pros and Cons and the Future. Korean Circ J. 2008;38:73-9.
Gupta K, Zhang J. Angiogenesis: a curse or cure. Postgrad Med J. 2005;81:236-42.
Nakagawa K, Chen YX, Yonemitsu Y, Murata T, Hata Y, Nakashima Y, et al. Angiogenesis and its regulation : roles of vascular endothelial cell growth factor. Semin Thromb Hemost. 2000;26:61-6.
Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol. 2004;164(6):1935-47.
Brem H, Erlich P, Tsakayannis D, Folkma J. Delay of wound healing by the angiogenesis inhibitor TNP-470. Surgical forum. 1997;48:714-6.
Gibran NS, Jang YC, Isik FF, Greenhalgh DG, Muffley LA, Underwood RA. Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J Surg Res. 2002;108:122-8.
Cho CH, Sung HK, Kim KT, Cheon HG, Hong HJ. COMP-angiopoetin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in diabetic mouse model. Proc Natl Acad Sci USA. 2006;103:4946-51.
Davis GE, Saunders WB. Molecular balance of capillary tube formation versus regression in wound repair: role of matrix metalloproteinases and their inhibitors. J Investig Dermatol Symp Proc. 2006;11:44-56.
Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The Role of Vascular Growth Factor in Wound Healing. J Surg Res. 2009;15:347-58.
Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117:1219-22.
Yla-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol. 2007;49:1015-26.
Banai S, Jaklitsch MT, Shou M, Lazarous DF, Scheinowitz M, Biro S, et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation. 1994;89:2183-9.
Takeshita S, Zhung L, Brogi E, Kearney M, Pu L-Q, Bunting S, et al. Therapeutic angiogenesis: a single intra-arterial bolus of vascular endothelial growth factor augments collateral vessel formation in a rabbit ischemic hindlimb model. J Clin Invest. 1994;93:662-70.
Takeshita S, Pu L-Q, Stein LA, Sniderman AD, Bunting S, Ferrara N, et al. Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation. 1994:90(Suppl II)228-34.
Takeshita S, Tsurumi Y, Couffinhal T, Asahara T, Bauters C, Symes JF, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest. 1996;75:487-502.
Pearlman JD, Hibberd MG, Chuang ML, Harada K, Lopez JJ, Gladstone SR, et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nature Med. 1995;1:1085-9.
Harada K, Friedman M, Lopez J, Wang S, Li J, Prasad PV, Pearlman JD, et al. Vascular endothelial growth factor in chronic myocardial ischemia. Am J Physiol. 1996;270:H1791-180.
Isner JM, Walsh K, Symes JF, Pieczek A, Takeshita S, Lowry J, et al. Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum Gene Ther.1996;7:859-88.
