Role of angiogenesis regulation in the process of scar formation

doi:10.3877/cma.j.issn.1673-9450.2019.04.013

Abstract

Abstract:

The regulation of angiogenesis mainly occurs in the last two stages of wound healing, namely the proliferation stage and the remodeling stage. Under normal circumstances, the wound forms a large number of disordered capillary beds, but with the gradual healing of the wound, most of the blood vessels apoptosis, degradation, and rearrangement, and finally returns to the normal structure and density. This process has been regulated by a series of complex molecules and signal pathways, including angiogenesis and anti-angiogenic factors. However, the questions about how wound vascular function and capillary hyperplasia affect scar formation have not been answered. This review summarizes the existing research results at home and abroad, comprehensively demonstrates the regulatory mechanism of wound angiogenesis, and discusses the relationship between angiogenesis and scar formation, as well as the potential mechanism of abnormal angiogensis affecting scar formation. This paper also introduces the related treatment schemes for angiogenesis, which provides a new idea for reducing scar formation.

Key words: Vascular endothelial growth factors, Wound healing, Cicatrix, Angiogenesis

Junyou Zhu, Shaohai Qi. Role of angiogenesis regulation in the process of scar formation[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2019, 14(04): 303-306.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhssyxfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1673-9450.2019.04.013

https://zhssyxfzz.cma-cmc.com.cn/EN/Y2019/V14/I04/303

References 54

[1]	Gurtner GC,Werner S,Barrandon Y, et al. Wound repair and regeneration[J]. Nature, 2008, 453(7193): 314-321.
[2]	Eming SA,Martin P,Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation[J]. Sci Transl Med, 2014, 6(265): 265sr266.
[3]	Battegay EJ. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects[J]. J Mol Med (Berl), 1995, 73(7): 333-346.
[4]	Benjamin LE. The controls of microvascular survival[J]. Cancer Metastasis Rev, 2000, 19(1/2): 75-81.
[5]	Dimmeler S,Zeiher, AM. Endothelial cell apoptosis in angiogenesis and vessel regression[J]. Circ Res, 2000, 87(6): 434-439.
[6]	Nissen NN,Polverini PJ,Koch AE, et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing[J]. Am J Pathol, 1998, 152(6): 1445-1452.
[7]	Cassell P. Review of article: Coadministration of adipose-derived stem cells and control-released basic fibroblast growth factor facilitates angiogenesis in a murine ischemic hind limb model by Horikoshi-Ishihara, Tobita, Tajima, et al. Journal of Vascular Surgery 12/2016；pp1825-1834[J]. J Vasc Nurs, 2017, 35(1): 36-37.
[8]	Uutela M,Wirzenius M,Paavonen K, et al. PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis[J]. Blood, 2004, 104(10): 3198-3204.
[9]	Pardali E,Goumans MJ,ten Dijke P. Signaling by members of the TGF-β family in vascular morphogenesis and disease[J]. Trends Cell Biol, 2010, 20(9): 556-567.
[10]	Michalczyk ER,Chen L,Fine D, et al. Pigment Epithelium-Derived Factor (PEDF) as a Regulator of Wound Angiogenesis[J]. Sci Rep, 2018, 8(1): 11142.
[11]	Wietecha MS,Chen L,Ranzer MJ, et al. Sprouty2 downregulates angiogenesis during mouse skin wound healing[J]. Am J Physiol Heart Circ Physiol, 2011, 300(2): H459-467.
[12]	Maclauchlan S,Skokos EA,Agah A, et al. Enhanced angiogenesis and reduced contraction in thrombospondin-2－null wounds is associated with increased levels of matrix metalloproteinases-2 and -9, and soluble VEGF[J]. J Histochem Cytochem, 2009, 57(4): 301-313.
[13]	Thomas H,Cowin AJ,Mills SJ. The Importance of Pericytes in Healing: Wounds and other Pathologies[J]. Int J Mol Sci, 2017, 18(6): pii: E1129.
[14]	Dulauroy S,Di Carlo SE,Langa F, et al. Lineage tracing and genetic ablation of ADAM12(＋) perivascular cells identify a major source of profibrotic cells during acute tissue injury[J]. Nat Med, 2012, 18(8): 1262-1270.
[15]	Ogawa R. High blood pressure (hypertension) may influence the results of clinical trials for scar and keloid treatments[J]. Plast Reconstr Surg, 2013, 132(6): 1074e-1075e.
[16]	付小兵，程飚. 病理性瘢痕治疗现状与展望[J]. 中华整形外科杂志，2006, 22(2): 146-149.
[17]	Zhang L,Qin H,Wu Z, et al. Identification of the potential targets for keloid and hypertrophic scar prevention[J]. J Dermatolog Treat, 2018, 29(6): 600-605.
[18]	Tonnesen MG,Feng X,Clark RA. Angiogenesis in wound healing[J]. J Investig Dermatol Symp Proc, 2000, 5(1): 40-46.
[19]	Eming SA,Brachvogel B,Odorisio T, et al. Regulation of angiogenesis: Wound healing as a model[J]. Prog Histochem Cytochem, 2008, 42(3): 115-170.
[20]	Jang YC,Arumugam S,Gibran NS, et al. Role of (v) integrins and angiogenesis during wound repair[J]. Wound Repair Regen, 2010, 7(5): 375-380.
[21]	Wilgus TA,Ferreira AM,Oberyszyn TM, et al. Regulation of scar formation by vascular endothelial growth factor[J]. Lab Invest, 2008, 88(6): 579-590.
[22]	沈锐，利天增，祁少海，等. 靶向血管治疗增生性瘢痕的实验研究[J]. 中华整形外科杂志，2003, 19(4): 254-257.
[23]	Fujiwara M,Muragaki Y,Ooshima A. Upregulation of transforming growth factor-β1 and vascular endothelial growth factor in cultured keloid fibroblasts: relevance to angiogenic activity[J]. Arch Dermatol Res, 2005, 297(4): 161-169.
[24]	Fujiwara M,Muragaki Y,Ooshima A. Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration[J]. Br J Dermatol, 2015, 153(2): 295-300.
[25]	Christopher G. Engeland. Stress, Aging, and Wound Healing[M]. New York: Springer, 2013.
[26]	Szpaderska AM,Zuckerman, JD,DiPietro LA. Differential Injury Responses in Oral Mucosal and Cutaneous Wounds[J]. J Dent Res, 2003, 82(8): 621-626.
[27]	姜笃银，付小兵，陈伟，等. 血管生成因子及其受体过表达与瘢痕疙瘩侵袭性生长[J]. 中华整形外科杂志，2004, 20(2): 128-131.
[28]	李高峰，罗成群，刘浔阳，等. 瘢痕内微循环的变化[J]. 中华医学美学美容杂志，2005, 11(4): 223-226.
[29]	van der Veer WM,Niessen FB,Ferreira JA, et al. Time course of the angiogenic response during normotrophic and hypertrophic scar formation in humans[J]. Wound Repair Regen, 2011, 19(3): 292-301.
[30]	Elpek GÖ. Angiogenesis and liver fibrosis[J]. World J Hepatol, 2015, 7(3): 377-391.
[31]	Farkas L,Gauldie J,Voelkel NF, et al. Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors[J]. Am J Respir Cell Mol Biol, 2011, 45(1): 1-15.
[32]	沈锐，利天增，祁少海，等. 血管内皮细胞生长因子在烧伤后肉芽组织和增生性瘢痕中的表达[J]. 中国康复理论与实践，2002, 8(1): 1-2.
[33]	Ren HT,Hu H,Li Y, et al. Endostatin inhibits hypertrophic scarring in a rabbit ear model[J]. J Zhejiang Univ Sci B, 2013, 14(3): 224-230.
[34]	Wietecha MS,Król MJ,Michalczyk ER, et al. Pigment epithelium-derived factor as a multifunctional regulator of wound healing[J]. Am J Physiol Heart Circ Physiol, 2015, 309(5): H812-826.
[35]	Nagy JA,Benjamin L,Zeng H, et al. Vascular permeability, vascular hyperpermeability and angiogenesis[J]. Angiogenesis, 2008, 11(2): 109-119.
[36]	Lingen MW. Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing[J]. Arch Pathol Lab Med, 2001, 125(1): 67-71.
[37]	Jackson CJ,Xue M,Thompson P. Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing[J]. Wound Repair Regen, 2005, 13(3): 284-294.
[38]	Mathai SK,Gulati M,Peng X, et al. Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype[J]. Lab Invest, 2010, 90(6): 812-823.
[39]	Laplante P,Sirois I,Raymond MA, et al. Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis[J]. Cell Death Differ, 2010, 17(2): 291-303.
[40]	Koh TJ,DiPietro LA. Inflammation and wound healing: the role of the macrophage[J]. Expert Rev Mol Med, 2011, 13: e23.
[41]	Wynn TA. Cellular and molecular mechanisms of fibrosis[J]. J Pathol, 2010, 214(2): 199-210.
[42]	Murray LA,Chen Q,Kramer MS, et al. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P[J]. Int J Biochem Cell Biol, 2011, 43(1): 154-162.
[43]	Perez-Aso M,Chiriboga L,Cronstein BN. Pharmacological blockade of adenosine A2A receptors diminishes scarring[J]. FASEB J, 2012, 26(10): 4254-4263.
[44]	Katebi M,Fernandez P,Chan ES, et al. Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, Bleomycin-induced Fibrosis[J]. Inflammation, 2008, 31(5): 299-303.
[45]	Hunt TK,Hopf H,Hussain Z. Physiology of wound healing[J]. Adv Skin Wound Care, 2000, 13(2 Suppl): 6-11.
[46]	Wong VW,Rustad KC,Akaishi S. et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling[J]. Nat Med, 2011, 18(1): 148-152.
[47]	Wong VW,Paterno J,Sorkin M, et al. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation[J]. FASEB J, 2011, 25(12): 4498-4510.
[48]	Li P,Li-Tsang CWP,Deng X, et al. The recovery of post-burn hypertrophic scar in a monitored pressure therapy intervention programme and the timing of intervention[J]. Burns, 2018, 44(6): 1451-1467.
[49]	Park TH,Park JH,Tirgan MH, et al. Reply: Outcomes of surgical excision with pressure therapy using magnets and identification of risk factors for recurrent keloids[J]. Plast Reconstr Surg, 2013, 132(4): 667e-668e.
[50]	van Leeuwen MC,van der Wal MB,Bulstra AE, et al. Intralesional cryotherapy for treatment of keloid scars: a prospective study[J]. Plast Reconstr Surg, 2015, 135(2): 580-589.
[51]	Har-Shai Y,Amar M,Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids[J]. Plast Reconstr Surg, 2003, 111(6): 1841-1852.
[52]	Sabry HH,Abdel Rahman SH,Hussein MS, et al. The Efficacy of Combining Fractional Carbon Dioxide Laser With Verapamil Hydrochloride or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Clinical and Immunohistochemical Study[J]. Dermatol Surg, 2019, 45(4): 536-546.
[53]	Zuccaro J,Ziolkowski N,Fish J. A Systematic Review of the Effectiveness of Laser Therapy for Hypertrophic Burn Scars[J]. Clin Plast Surg, 2017, 44(4): 767-779.
[54]	Diao JS,Xia WS,Guo SZ. Bevacizumab: A potential agent for prevention and treatment of hypertrophic scar[J]. Burns, 2010, 36(7): 1136-1137.

Please choose a citation manager

Content to export