Skip to main content

Advertisement

SpringerLink
Log in

Angiogenesis in Wound Healing following Pharmacological and Toxicological Exposures

  • Wound Healing and Tissue Repair (C Yates and R Mota, Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

Toxicological and pharmacological exposures may accelerate or impede wound healing and tissue repair. These exposures impact the wound healing cascade and steps within the process including (1) hemostasis, (2) the inflammatory stage, (3) proliferation, and (4) maturation. Angiogenesis plays a critical role during the wound healing process via clot invasion and organization of vasculature throughout new connective tissue. This review examines how toxicological insults and pharmacotherapeutics impact the tissue healing process. We focus on four primary environmental exposures, namely, radiation, pharmacotherapeutics, metals, and dioxins for the scope of this review.

Recent Findings

Recent literature suggests that individuals with comorbidities such as autoimmune disorders or cardiometabolic diseases are most susceptible to angiogenic delays and wound healing deficits following toxicological or pharmacological insult. As newer drug-delivery systems and pharmaceutics become available, exposures to these compounds have led to improved wound healing by impacting molecular angiogenic pathways. Environmental and medical exposures from radiological or persistent pollutants may impede wound healing via these angiogenic factors.

Summary

These data suggest that environmental exposures via metals, dioxins, exogenous radiation, or pharmaceutics will ultimately promote or diminish molecular angiogenic factors, such as vascular endothelial growth factor (VEGF), and impact the wound healing cascade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Stechmiller JK. Understanding the role of nutrition and wound healing. Nutr Clin Pract. 2010;25(1):61–8.

    PubMed  Google Scholar 

  2. Zinder R, Cooley R, Vlad LG, Molnar JA. Vitamin A and wound healing. Nutr Clin Pract. 2019;34(6):839–49.

    PubMed  Google Scholar 

  3. Chiaverina G, di Blasio L, Monica V, Accardo M, Palmiero M, Peracino B, et al. Dynamic interplay between pericytes and endothelial cells during sprouting angiogenesis. Cells. 2019;8(9).

  4. Bazmara H, Soltani M, Sefidgar M, Bazargan M, Mousavi Naeenian M, Rahmim A. Blood flow and endothelial cell phenotype regulation during sprouting angiogenesis. Med Biol Eng Comput. 2016;54(2–3):547–58.

    PubMed  Google Scholar 

  5. Gremmel T, Frelinger AL 3rd, Michelson AD. Platelet physiology. Semin Thromb Hemost. 2016;42(3):191–204.

    CAS  PubMed  Google Scholar 

  6. Hvas AM. Platelet function in thrombosis and hemostasis. Semin Thromb Hemost. 2016;42(3):183–4.

    PubMed  Google Scholar 

  7. Olas B, Bryś M. Effects of coffee, energy drinks and their components on hemostasis: the hypothetical mechanisms of their action. Food Chem Toxicol. 2019;127:31–41.

    CAS  PubMed  Google Scholar 

  8. Varner JA. The sticky truth about angiogenesis and thrombospondins. J Clin Invest. 2006;116(12):3111–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Rao SP, Sikora L, Hosseinkhani MR, Pinkerton KE, Sriramarao P. Exposure to environmental tobacco smoke induces angiogenesis and leukocyte trafficking in lung microvessels. Exp Lung Res. 2009;35(2):119–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, et al. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 pathway. Environ Health Perspect. 2014;122(3):255–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. El-Masri H, Kleinstreuer N, Hines RN, Adams L, Tal T, Isaacs K, et al. Integration of life-stage physiologically based pharmacokinetic models with adverse outcome pathways and environmental exposure models to screen for environmental hazards. Toxicol Sci. 2016;152(1):230–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhu W, London NR, Gibson CC, Davis CT, Tong Z, Sorensen LK, et al. Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability. Nature. 2012;492(7428):252–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Sun X, Shi J, Zou X, Wang C, Yang Y, Zhang H. Silver nanoparticles interact with the cell membrane and increase endothelial permeability by promoting VE-cadherin internalization. J Hazard Mater. 2016;317:570–8.

    CAS  PubMed  Google Scholar 

  14. Li TH, Huang CC, Yang YY, Lee KC, Hsieh SL, Hsieh YC, et al. Thalidomide improves the intestinal mucosal injury and suppresses mesenteric angiogenesis and vasodilatation by down-regulating inflammasomes-related cascades in cirrhotic rats. PLoS One. 2016;11(1):e0147212.

    PubMed  PubMed Central  Google Scholar 

  15. Kimball A, Schaller M, Joshi A, Davis FM, denDekker A, Boniakowski A, et al. Ly6C(Hi) blood monocyte/macrophage drive chronic inflammation and impair wound healing in diabetes mellitus. Arterioscler Thromb Vasc Biol. 2018;38(5):1102–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330(6002):362–6.

    CAS  PubMed  Google Scholar 

  17. Bauer SM, Bauer RJ, Velazquez OC. Angiogenesis, vasculogenesis, and induction of healing in chronic wounds. Vasc Endovasc Surg. 2005;39(4):293–306.

    Google Scholar 

  18. Keeley EC, Mehrad B, Strieter RM. Chemokines as mediators of neovascularization. Arterioscler Thromb Vasc Biol. 2008;28(11):1928–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Steinritz D, Schmidt A, Balszuweit F, Thiermann H, Ibrahim M, Bölck B, et al. Assessment of endothelial cell migration after exposure to toxic chemicals. J Vis Exp. 2015;101:e52768.

    Google Scholar 

  20. Ku YH, Cho BJ, Kim MJ, Lim S, Park YJ, Jang HC, et al. Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation. BMC Pharmacol Toxicol. 2017;18(1):62.

    PubMed  PubMed Central  Google Scholar 

  21. • Krausz AE, Adler BL, Cabral V, Navati M, Doerner J, Charafeddine RA, et al. Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine. 2015;11(1):195–206. Nanoparticles act as therapeutic agents for wound healing.

  22. Ji C, Yue S, Gu J, Kong Y, Chen H, Yu C, et al. 2, 7-Dibromocarbazole interferes with tube formation in HUVECs by altering Ang2 promoter DNA methylation status. Sci Total Environ. 2019;697:134156.

    CAS  PubMed  Google Scholar 

  23. Tanha S, Rafiee-Tehrani M, Abdollahi M, Vakilian S, Esmaili Z, Naraghi ZS, et al. G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo. J Biomed Mater Res A. 2017;105(10):2830–42.

    CAS  PubMed  Google Scholar 

  24. Zubair M. Prevalence and interrelationships of foot ulcer, risk-factors and antibiotic resistance in foot ulcers in diabetic populations: a systematic review and meta-analysis. World J Diabetes. 2020;11(3):78–89.

    PubMed  PubMed Central  Google Scholar 

  25. Ren X, Han Y, Wang J, Jiang Y, Yi Z, Xu H, et al. An aligned porous electrospun fibrous membrane with controlled drug delivery-an efficient strategy to accelerate diabetic wound healing with improved angiogenesis. Acta Biomater. 2018;70:140–53.

    CAS  PubMed  Google Scholar 

  26. Gorgulho CM, Romagnoli GG, Bharthi R, Lotze MT. Johnny on the spot-chronic inflammation is driven by HMGB1. Front Immunol. 2019;10:1561.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Tenkate T, Adam B, Al-Rifai RH, Chou BR, Gobba F, Ivanov ID, et al. WHO/ILO work-related burden of disease and injury: protocol for systematic reviews of occupational exposure to solar ultraviolet radiation and of the effect of occupational exposure to solar ultraviolet radiation on cataract. Environ Int 2019.

  28. Hasan H, Muhammed T, Yu J, Taguchi K, Samargandi OA, Howard AF, et al. Assessing the methodological quality of systematic reviews in radiation oncology: a systematic review. Cancer Epidemiol. 2017;50(Pt A):141–9.

    PubMed  Google Scholar 

  29. D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci. 2013;14(6):12222–48.

    PubMed  PubMed Central  Google Scholar 

  30. Pillai S, Oresajo C, Hayward J. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation–a review. Int J Cosmet Sci. 2005;27(1):17–34.

    CAS  PubMed  Google Scholar 

  31. Shetty PK, Venuvanka V, Jagani HV, Chethan GH, Ligade VS, Musmade PB, et al. Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity. Int J Nanomed. 2015;10:6477–91.

    CAS  Google Scholar 

  32. Yu BB, Zhi H, Zhang XY, Liang JW, He J, Su C, et al. Mitochondrial dysfunction-mediated decline in angiogenic capacity of endothelial progenitor cells is associated with capillary rarefaction in patients with hypertension via downregulation of CXCR4/JAK2/SIRT5 signaling. EBioMedicine. 2019;42:64–75.

    PubMed  PubMed Central  Google Scholar 

  33. Ungvari Z, Tarantini S, Kiss T, Wren JD, Giles CB, Griffin CT, et al. Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. Nat Rev Cardiol. 2018;15(9):555–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Trend S, Jones AP, Cha L, Cooper MN, Geldenhuys S, Fabis-Pedrini MJ, et al. Short-term changes in frequencies of circulating leukocytes associated with narrowband UVB phototherapy in people with clinically isolated syndrome. Sci Rep. 2019;9(1):7980.

    PubMed  PubMed Central  Google Scholar 

  35. McGonigle TA, Keane KN, Ghaly S, Carter KW, Anderson D, Scott NM, et al. UV irradiation of skin enhances glycolytic flux and reduces migration capabilities in bone marrow-differentiated dendritic cells. Am J Pathol. 2017;187(9):2046–59.

    CAS  PubMed  Google Scholar 

  36. Bearden JA. X-ray wavelengths. Rev Mod Phys. 1967;39(1):78.

    CAS  Google Scholar 

  37. Yang Y, Zhang L, Cai J, Li X, Cheng D, Su H, et al. Tumor angiogenesis targeted radiosensitization therapy using gold nanoprobes guided by MRI/SPECT imaging. ACS Appl Mater Interfaces. 2016;8(3):1718–32.

    CAS  PubMed  Google Scholar 

  38. Martin BJ. Inhibiting vasculogenesis after radiation: a new paradigm to improve local control by radiotherapy. Semin Radiat Oncol. 2013;23(4):281–7.

    PubMed  Google Scholar 

  39. • Powathil GG, Munro AJ, Chaplain MA, Swat M. Bystander effects and their implications for clinical radiation therapy: insights from multiscale in silico experiments. J Theor Biol. 2016;401:1–14. Bystander responses are key in mediating radiation damage to cells at low-doses of radiotherapy.

  40. Jabbari N, Nawaz M, Rezaie J. Bystander effects of ionizing radiation: conditioned media from X-ray irradiated MCF-7 cells increases the angiogenic ability of endothelial cells. Cell Commun Signal. 2019;17(1):165.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhao C, Wang H, Xiong C, Liu Y. Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood-brain barrier. Biochem Biophys Res Commun. 2018;502(3):324–31.

    CAS  PubMed  Google Scholar 

  42. Marques FG, Poli E, Rino J, Pinto MT, Diegues I, Pina F, et al. Low doses of ionizing radiation enhance the angiogenic potential of adipocyte conditioned medium. Radiat Res. 2019;192(5):517–26.

    CAS  PubMed  Google Scholar 

  43. Teresa Pinto A, Laranjeiro Pinto M, Patrícia Cardoso A, Monteiro C, Teixeira Pinto M, Filipe Maia A, et al. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Sci Rep. 2016;6:18765.

    PubMed  PubMed Central  Google Scholar 

  44. Baselet B, Sonveaux P, Baatout S, Aerts A. Pathological effects of ionizing radiation: endothelial activation and dysfunction. Cell Mol Life Sci. 2019;76(4):699–728.

    CAS  PubMed  Google Scholar 

  45. Donneys A, Nelson NS, Perosky JE, Polyatskaya Y, Rodriguez JJ, Figueredo C, et al. Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation. Bone. 2016;84:245–52.

    CAS  PubMed  Google Scholar 

  46. González-González A, González A, Rueda N, Alonso-González C, Menéndez-Menéndez J, Gómez-Arozamena J, et al. Melatonin enhances the usefulness of ionizing radiation: involving the regulation of different steps of the angiogenic process. Front Physiol. 2019;10:879.

    PubMed  PubMed Central  Google Scholar 

  47. Boccardo S, Gaudiello E, Melly L, Cerino G, Ricci D, Martin I, et al. Engineered mesenchymal cell-based patches as controlled VEGF delivery systems to induce extrinsic angiogenesis. Acta Biomater. 2016;42:127–35.

    CAS  PubMed  Google Scholar 

  48. Protopsaltis NJ, Liang W, Nudleman E, Ferrara N. Interleukin-22 promotes tumor angiogenesis. Angiogenesis. 2019;22(2):311–23.

    CAS  PubMed  Google Scholar 

  49. Yang D, Jin C, Ma H, Huang M, Shi GP, Wang J, et al. EphrinB2/EphB4 pathway in postnatal angiogenesis: a potential therapeutic target for ischemic cardiovascular disease. Angiogenesis. 2016;19(3):297–309.

    CAS  PubMed  Google Scholar 

  50. Öhnstedt E, Lofton Tomenius H, Vågesjö E, Phillipson M. The discovery and development of topical medicines for wound healing. Expert Opin Drug Discovery. 2019;14(5):485–97.

    Google Scholar 

  51. Ziegler ME, Hatch MM, Wu N, Muawad SA, Hughes CC. mTORC2 mediates CXCL12-induced angiogenesis. Angiogenesis. 2016;19(3):359–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. •• Cambiaso-Daniel J, Boukovalas S, Bitz GH, Branski LK, Herndon DN, Culnan DM. Topical antimicrobials in burn care: part I–topical antiseptics. Ann Plast Surg. 2018. This review provides a summary for topical antiseptics including current clinical use and mechanisms, in addition to advantages and disadvantages of antiseptic compounds.

  53. Totoraitis K, Cohen JL, Friedman A. Topical approaches to improve surgical outcomes and wound healing: a review of efficacy and safety. J Drugs Dermatol: JDD. 2017;16(3):209–12.

    CAS  PubMed  Google Scholar 

  54. Lu M, Hansen EN. Hydrogen peroxide wound irrigation in orthopaedic surgery. J Bone Joint Infect. 2017;2(1):3.

    Google Scholar 

  55. Summa M, Russo D, Penna I, Margaroli N, Bayer IS, Bandiera T, et al. A biocompatible sodium alginate/povidone iodine film enhances wound healing. Eur J Pharm Biopharm. 2018;122:17–24.

    CAS  PubMed  Google Scholar 

  56. Zhou M, Song X, Huang Y, Wei L, Li Z, You Q, et al. Wogonin inhibits H2O2-induced angiogenesis via suppressing PI3K/Akt/NF-κB signaling pathway. Vasc Pharmacol. 2014;60(3):110–9.

    CAS  Google Scholar 

  57. Kim YM, Kim SJ, Tatsunami R, Yamamura H, Fukai T, Ushio-Fukai M. ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. Am J Phys Cell Phys. 2017;312(6):C749–c64.

    Google Scholar 

  58. Loo AE, Wong YT, Ho R, Wasser M, Du T, Ng WT, et al. Effects of hydrogen peroxide on wound healing in mice in relation to oxidative damage. PLoS One. 2012;7(11):e49215.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Roy S, Khanna S, Nallu K, Hunt TK, Sen CK. Dermal wound healing is subject to redox control. Mol Ther. 2006;13(1):211–20.

    CAS  PubMed  Google Scholar 

  60. Lee Y, Son JY, Kang JI, Park KM, Park KD. Hydrogen peroxide-releasing hydrogels for enhanced endothelial cell activities and neovascularization. ACS Appl Mater Interfaces. 2018;10(21):18372–9.

    CAS  PubMed  Google Scholar 

  61. Pak CS, Park DH, Oh TS, Lee WJ, Jun YJ, Lee KA, et al. Comparison of the efficacy and safety of povidone-iodine foam dressing (Betafoam), hydrocellular foam dressing (Allevyn), and petrolatum gauze for split-thickness skin graft donor site dressing. Int Wound J. 2019;16(2):379–86.

    PubMed  Google Scholar 

  62. Jung JA, Han SK, Jeong SH, Dhong ES, Park KG, Kim WK. In vitro evaluation of Betafoam, a new polyurethane foam dressing. Adv Skin Wound Care. 2017;30(6):262–71.

    PubMed  Google Scholar 

  63. Lee JW, Song KY. Evaluation of a polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam) in a rat wound model. Ann Surg Treat Res. 2018;94(1):1–7.

    CAS  PubMed  Google Scholar 

  64. Gwak HC, Han SH, Lee J, Park S, Sung KS, Kim HJ, et al. Efficacy of a povidone-iodine foam dressing (Betafoam) on diabetic foot ulcer. Int Wound J. 2020;17(1):91–9.

    PubMed  Google Scholar 

  65. Schoos A, Gabriel C, Knab VM, Fux DA. Activation of HIF-1α by δ-opioid receptors induces COX-2 expression in breast cancer cells and leads to paracrine activation of vascular endothelial cells. J Pharmacol Exp Ther. 2019;370(3):480–9.

    CAS  PubMed  Google Scholar 

  66. Gupta M, Poonawala T, Farooqui M, Ericson ME, Gupta K. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats. J Diabetes. 2015;7(4):573–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Gürsoy K, Oruç M, Kankaya Y, Ulusoy MG, Koçer U, Kankaya D, et al. Effect of topically applied sildenafil citrate on wound healing: experimental study. Bosn J Basic Med Sci. 2014;14(3):125–31.

    PubMed  PubMed Central  Google Scholar 

  68. Farsaei S, Khalili H, Farboud ES, Khazaeipour Z. Sildenafil in the treatment of pressure ulcer: a randomised clinical trial. Int Wound J. 2015;12(1):111–7.

    PubMed  Google Scholar 

  69. Veith AP, Henderson K, Spencer A, Sligar AD, Baker AB. Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev. 2019;146:97–125.

    CAS  PubMed  Google Scholar 

  70. Trenti A, Zulato E, Pasqualini L, Indraccolo S, Bolego C, Trevisi L. Therapeutic concentrations of digitoxin inhibit endothelial focal adhesion kinase and angiogenesis induced by different growth factors. Br J Pharmacol. 2017;174(18):3094–106.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Cui HS, Joo SY, Lee DH, Yu JH, Jeong JH, Kim J-B, et al. Low temperature plasma induces angiogenic growth factor via up-regulating hypoxia–inducible factor 1α in human dermal fibroblasts. Arch Biochem Biophys. 2017;630:9–17.

    CAS  PubMed  Google Scholar 

  72. Serena TE, Fife CE, Eckert KA, Yaakov RA, Carter MJ. A new approach to clinical research: integrating clinical care, quality reporting, and research using a wound care network-based learning healthcare system. Wound Repair Regen. 2017;25(3):354–65.

    PubMed  Google Scholar 

  73. Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg. 1995;21(1):71–8 discussion 9-81.

    CAS  PubMed  Google Scholar 

  74. Wieman TJ, Mercke YK, Cerrito PB, Taber SW. Resection of the metatarsal head for diabetic foot ulcers. Am J Surg. 1998;176(5):436–41.

    CAS  PubMed  Google Scholar 

  75. Xie Z, Paras CB, Weng H, Punnakitikashem P, Su LC, Vu K, et al. Dual growth factor releasing multi-functional nanofibers for wound healing. Acta Biomater. 2013;9(12):9351–9.

    CAS  PubMed  Google Scholar 

  76. Lai HJ, Kuan CH, Wu HC, Tsai JC, Chen TM, Hsieh DJ, et al. Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing. Acta Biomater. 2014;10(10):4156–66.

    CAS  PubMed  Google Scholar 

  77. Sriramulu S, Banerjee A, Di Liddo R, Jothimani G, Gopinath M, Murugesan R, et al. Concise review on clinical applications of conditioned medium derived from human umbilical cord-mesenchymal stem cells (UC-MSCs). Int J Hematol Oncol Stem Cell Res. 2018;12(3):230–4.

    PubMed  PubMed Central  Google Scholar 

  78. Shen C, Lie P, Miao T, Yu M, Lu Q, Feng T, et al. Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis. Mol Med Rep. 2015;12(1):20–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Arutyunyan I, Fatkhudinov T, Kananykhina E, Usman N, Elchaninov A, Makarov A, et al. Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study. Stem Cell Res Ther. 2016;7:46.

    PubMed  PubMed Central  Google Scholar 

  80. Dhall S, Silva JP, Liu Y, Hrynyk M, Garcia M, Chan A, et al. Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats. Clin Sci (Lond). 2015;129(12):1115–29.

    CAS  Google Scholar 

  81. Oryan A, Alemzadeh E. Effects of insulin on wound healing: a review of animal and human evidences. Life Sci. 2017;174:59–67.

    CAS  PubMed  Google Scholar 

  82. Giri P, Ebert S, Braumann UD, Kremer M, Giri S, Machens HG, et al. Skin regeneration in deep second-degree scald injuries either by infusion pumping or topical application of recombinant human erythropoietin gel. Drug Des Devel Ther. 2015;9:2565–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Hamed S, Ullmann Y, Egozi D, Keren A, Daod E, Anis O, et al. Topical erythropoietin treatment accelerates the healing of cutaneous burn wounds in diabetic pigs through an aquaporin-3-dependent mechanism. Diabetes. 2017;66(8):2254–65.

    CAS  PubMed  Google Scholar 

  84. Meaney C, Rhebergen S, Kohandel M. In silico analysis of hypoxia activated prodrugs in combination with anti angiogenic therapy through nanocell delivery. PLoS Comput Biol. 2020;16(5):e1007926.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Halasz K, Kelly SJ, Iqbal MT, Pathak Y, Sutariya V. Utilization of apatinib-loaded nanoparticles for the treatment of ocular neovascularization. Current drug delivery. 2019;16(2):153–63.

    CAS  PubMed  Google Scholar 

  86. e Silva RL, Kanan Y, Mirando AC, Kim J, Shmueli RB, Lorenc VE, et al. Tyrosine kinase blocking collagen IV–derived peptide suppresses ocular neovascularization and vascular leakage. Sci Transl Med. 2017;9(373):eaai8030.

    Google Scholar 

  87. Ahn JW, Shalabi D, Correa-Selm LM, Dasgeb B, Nikbakht N, Cha J. Impaired wound healing secondary to bevacizumab. Int Wound J. 2019;16(4):1009–12.

    PubMed  Google Scholar 

  88. Tan C, Ellingson B, Yao J. CEST used to monitor bevacizumab treatment against glioblastoma. 2018.

  89. Toy BC, Schachar IH, Tan GS, Moshfeghi DM. Chronic vascular arrest as a predictor of bevacizumab treatment failure in retinopathy of prematurity. Ophthalmology. 2016;123(10):2166–75.

    PubMed  Google Scholar 

  90. Liu J, Zhang X, Li G, Xu F, Li S, Teng L, et al. Anti-angiogenic activity of bevacizumab-bearing dexamethasone-loaded PLGA nanoparticles for potential intravitreal applications. Int J Nanomedicine. 2019;14:8819–34.

    PubMed  PubMed Central  Google Scholar 

  91. Schneider MK, Ioanas HI, Xandry J, Rudin M. An in vivo wound healing model for the characterization of the angiogenic process and its modulation by pharmacological interventions. Sci Rep. 2019;9(1):6004.

    PubMed  PubMed Central  Google Scholar 

  92. Plotkin S, Tonsgard J, Ullrich N, Allen J, Blakeley J, Rosser T, et al. RARE-19. Multicenter, PHase 2 study of bevacizumab in children and adults with neurofibromatosis 2 and progressive vestibular schwannomas: an NF Clinical Trials Consortium Study. Neuro-oncology. 2017;19(Suppl 6):vi215.

    PubMed Central  Google Scholar 

  93. Dong M, Di G, Zhang X, Zhou Q, Shi W. Subconjunctival bevacizumab injection impairs corneal innervations and epithelial wound healing in mice. Invest Ophthalmol Vis Sci. 2017;58(3):1469–77.

    CAS  PubMed  Google Scholar 

  94. Eren K, Turgut B, Akin MM, Demir T. The suppression of wound healing response with sirolimus and sunitinib following experimental trabeculectomy in a rabbit model. Curr Eye Res. 2016;41(3):367–76.

    CAS  PubMed  Google Scholar 

  95. Klettner A, Tahmaz N, Dithmer M, Richert E, Roider J. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br J Ophthalmol. 2014;98(10):1448–52.

    PubMed  Google Scholar 

  96. Zhang H, Huang Z, Zou X, Liu T. Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. 2016;7(50):82473–81.

    PubMed  PubMed Central  Google Scholar 

  97. Miraftabi A, Nilforushan N. Wound dehiscence and device migration after subconjunctival bevacizumab injection with Ahmed glaucoma valve implantation. Journal of ophthalmic & vision research. 2016;11(1):112.

    Google Scholar 

  98. Crispel Y, Ghanem S, Attias J, Kogan I, Brenner B, Nadir Y. Involvement of the heparanase procoagulant domain in bleeding and wound healing. J Thromb Haemost. 2017;15(7):1463–72.

    CAS  PubMed  Google Scholar 

  99. Chen X, Jiang W, Yue C, Zhang W, Tong C, Dai D, et al. Heparanase contributes to trans-endothelial migration of hepatocellular carcinoma cells. J Cancer. 2017;8(16):3309.

    PubMed  PubMed Central  Google Scholar 

  100. Kamath PR, Sunil D, Joseph MM, Salam AAA, Sreelekha T. Indole-coumarin-thiadiazole hybrids: an appraisal of their MCF-7 cell growth inhibition, apoptotic, antimetastatic and computational Bcl-2 binding potential. Eur J Med Chem. 2017;136:442–51.

    CAS  PubMed  Google Scholar 

  101. Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Mileusnic D, Kataranovski D, et al. Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats. Cutan Ocul Toxicol. 2017;36(3):283–8.

    CAS  PubMed  Google Scholar 

  102. Ismael H, Horst M, Farooq M, Jordon J, Patton JH, Rubinfeld IS. Adverse effects of preoperative steroid use on surgical outcomes. Am J Surg. 2011;201(3):305–8 discussion 8-9.

    CAS  PubMed  Google Scholar 

  103. Slominski AT, Zmijewski MA. Glucocorticoids inhibit wound healing: novel mechanism of action. J Invest Dermatol. 2017;137(5):1012–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Gastaldello A, Livingstone DE, Abernethie AJ, Tsang N, Walker BR, Hadoke PW, et al. Safer topical treatment for inflammation using 5α-tetrahydrocorticosterone in mouse models. Biochem Pharmacol. 2017;129:73–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Carolina E, Kato T, Khanh VC, Moriguchi K, Yamashita T, Takeuchi K, et al. Glucocorticoid impaired the wound healing ability of endothelial progenitor cells by reducing the expression of CXCR4 in the PGE2 pathway. Front Med (Lausanne). 2018;5:276.

    Google Scholar 

  106. Zhang B, Zhu X, Wang L, Hao S, Xu X, Niu F, et al. Dexamethasone impairs neurofunctional recovery in rats following traumatic brain injury by reducing circulating endothelial progenitor cells and angiogenesis. Brain Res. 2019;1725:146469.

    CAS  PubMed  Google Scholar 

  107. Shrestha S, Eldridge M, Cortes M, Singh P, Kim M-J, Gladding R, et al. W1. Novel Pet radioligands show that COX-1 is constitutively expressed and that COX-2 is induced by inflammation in rhesus monkey brain. Neuropsychopharmacology. 2016;41:S455–630.

    Google Scholar 

  108. Yang H-H, Duan J-X, Liu S-K, Xiong J-B, Guan X-X, Zhong W-J, et al. A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation. Theranostics. 2020;10(11):4749.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Goren I, Lee SY, Maucher D, Nüsing R, Schlich T, Pfeilschifter J, et al. Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE(2) formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds. Int Wound J. 2017;14(1):53–63.

    PubMed  Google Scholar 

  110. Reisinger KW, Schellekens DH, Bosmans JW, Boonen B, Hulsewé KW, Sastrowijoto P, et al. Cyclooxygenase-2 is essential for colorectal anastomotic healing. Ann Surg. 2017;265(3):547–54.

    PubMed  Google Scholar 

  111. Ramirez-Garcia-Luna JL, Wong TH, Chan D, Al-Saran Y, Awlia A, Abou-Rjeili M, et al. Defective bone repair in diclofenac treated C57Bl6 mice with and without lipopolysaccharide induced systemic inflammation. J Cell Physiol. 2019;234(3):3078–87.

    CAS  PubMed  Google Scholar 

  112. Gorissen KJ, Benning D, Berghmans T, Snoeijs MG, Sosef MN, Hulsewe KW, et al. Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery. Br J Surg. 2012;99(5):721–7.

    CAS  PubMed  Google Scholar 

  113. Klifto KM, Major MR, Barone AAL, Payne RM, Elhelali A, Seal SM, et al. Perioperative systemic nonsteroidal anti-inflammatory drugs (NSAIDs) in women undergoing breast surgery. Cochrane Database of Systematic Reviews. 2019(3).

  114. Estrella-Mendoza MF, Jiménez-Gómez F, López-Ornelas A, Pérez-Gutiérrez RM, Flores-Estrada J. Cucurbita argyrosperma seed extracts attenuate angiogenesis in a corneal chemical burn model. Nutrients. 2019;11(5).

  115. Kiani K, Rudzitis-Auth J, Scheuer C, Movahedin M, Sadati Lamardi SN, Malekafzali Ardakani H, et al. Calligonum comosum (Escanbil) extract exerts anti-angiogenic, anti-proliferative and anti-inflammatory effects on endometriotic lesions. J Ethnopharmacol. 2019;239:111918.

    CAS  PubMed  Google Scholar 

  116. Dai F, Gao L, Zhao Y, Wang C, Xie S. Farrerol inhibited angiogenesis through Akt/mTOR, Erk and Jak2/Stat3 signal pathway. Phytomedicine. 2016;23(7):686–93.

    CAS  PubMed  Google Scholar 

  117. Varol M. Anti-breast cancer and anti-angiogenic potential of a lichen-derived small-molecule: barbatolic acid. Cytotechnology. 2018;70(6):1565–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Wu H, He L, Shi J, Hou X, Zhang H, Zhang X, et al. Resveratrol inhibits VEGF-induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation. Clin Exp Pharmacol Physiol. 2018;45(12):1265–73.

    CAS  PubMed  Google Scholar 

  119. Kim K, Heo Y-K, Chun S, Kim C-H, Bian Y, Bae O-N, et al. Arsenic may act as a pro-metastatic carcinogen through promoting tumor cell-induced platelet aggregation. Toxicol Sci. 2019;168(1):18–27.

    CAS  PubMed  Google Scholar 

  120. Wang Y, Yin D, Xu C, Wang K, Zheng L, Zhang Y. Roxarsone induces angiogenesis via PI3K/Akt signaling. Cell Biosci. 2016;6:54.

    PubMed  PubMed Central  Google Scholar 

  121. Pinto BI, Lujan OR, Ramos SA, Propper CR, Kellar RS. Estrogen mitigates the negative effects of arsenic contamination in an in vitro wound model. Appl In Vitro Toxicol. 2018;4(1):24–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Wei T, Jia J, Wada Y, Kapron CM, Liu J. Dose dependent effects of cadmium on tumor angiogenesis. Oncotarget. 2017;8(27):44944–59.

    PubMed  PubMed Central  Google Scholar 

  123. Mei H, Yao P, Wang S, Li N, Zhu T, Chen X, et al. Chronic low-dose cadmium exposure impairs cutaneous wound healing with defective early inflammatory responses after skin injury. Toxicol Sci. 2017;159(2):327–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Rath G, Hussain T, Chauhan G, Garg T, Goyal AK. Collagen nanofiber containing silver nanoparticles for improved wound-healing applications. J Drug Target. 2016;24(6):520–9.

    CAS  PubMed  Google Scholar 

  125. Kumar SSD, Rajendran NK, Houreld NN, Abrahamse H. Recent advances on silver nanoparticle and biopolymer-based biomaterials for wound healing applications. Int J Biol Macromol. 2018;115:165–75.

    CAS  PubMed  Google Scholar 

  126. Avalos A, Haza AI, Mateo D, Morales P. Interactions of manufactured silver nanoparticles of different sizes with normal human dermal fibroblasts. Int Wound J. 2016;13(1):101–9.

    PubMed  Google Scholar 

  127. Franková J, Pivodová V, Vágnerová H, Juráňová J, Ulrichová J. Effects of silver nanoparticles on primary cell cultures of fibroblasts and keratinocytes in a wound-healing model. J Appl Biomater Funct Mater. 2016;14(2):e137–42.

    PubMed  Google Scholar 

  128. Shao J, Wang B, Li J, Jansen JA, Walboomers XF, Yang F. Antibacterial effect and wound healing ability of silver nanoparticles incorporation into chitosan-based nanofibrous membranes. Mater Sci Eng C. 2019;98:1053–63.

    CAS  Google Scholar 

  129. Rather HA, Jhala D, Vasita R. Dual functional approaches for osteogenesis coupled angiogenesis in bone tissue engineering. Mater Sci Eng C 2019:109761.

  130. Guo S, Zhang R, Liu Q, Wan Q, Wang Y, Yu Y, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes injury-induced vascular neointima formation in mice. FASEB J. 2019;33(9):10207–17.

    CAS  PubMed  Google Scholar 

  131. Barouti N, Mainetti C, Fontao L, Sorg O. L-Tryptophan as a novel potential pharmacological treatment for wound healing via aryl hydrocarbon receptor activation. Dermatology. 2015;230(4):332–9.

    CAS  PubMed  Google Scholar 

  132. Kalkunte S, Huang Z, Lippe E, Kumar S, Robertson LW, Sharma S. Polychlorinated biphenyls target Notch/Dll and VEGF R2 in the mouse placenta and human trophoblast cell lines for their anti-angiogenic effects. Sci Rep. 2017;7:39885.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by NIH grants K99 ES029104 and R00 ES029104.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of New Mexico-Health Sciences Center, Albuquerque, NM, 87131, USA

    Russell Hunter

  2. College of Nursing, University of New Mexico-Health Sciences Center, MSC09 5360, Albuquerque, NM, 87131, USA

    Katie T. Kivlighan, Sharon Ruyak, Quiteria Jacquez & Katherine E. Zychowski

Authors
  1. Russell Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katie T. Kivlighan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharon Ruyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Quiteria Jacquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katherine E. Zychowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katherine E. Zychowski.

Ethics declarations

Conflict of Interest

All authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Wound Healing and Tissue Repair

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hunter, R., Kivlighan, K.T., Ruyak, S. et al. Angiogenesis in Wound Healing following Pharmacological and Toxicological Exposures. Curr Pathobiol Rep 8, 99–109 (2020). https://doi.org/10.1007/s40139-020-00212-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40139-020-00212-y

Keywords

Search

Navigation