Browse > Article

Effect of verapamil on VEGF expression and apoptosis in early wound scarring of the rabbit ear  

Bae, Tae Hui (Department of Plastic and Reconstructive Surgery, Pathology, College of Medicine, Chung-Ang University)
Kim, Woo Seob (Department of Plastic and Reconstructive Surgery, Pathology, College of Medicine, Chung-Ang University)
Kim, Han Koo (Department of Plastic and Reconstructive Surgery, Pathology, College of Medicine, Chung-Ang University)
Kim, Mi Kyoung (Department of Plastic and Reconstructive Surgery, Pathology, College of Medicine, Chung-Ang University)
Publication Information
Archives of Plastic Surgery / v.36, no.1, 2009 , pp. 11-18 More about this Journal
Abstract
Purpose: Excessive scarring in the forms of keloid and hypertrophic scar could be a consquence of the accumulation of granulation tissue cells due to aberrant control of apoptosis. Verapamil retard extracelluar matrix production and inhibits VEGF production in primary cultured keloid fibroblast. The object of this study was effect of verapamil on VEGF expression and apoptosis in early wound scarring of the rabbit ear. Methods: Full thickness wounds were created on the ventral side of 6 New Zealand rabbits's ear. 16 days after initial wounding verapamil and saline were injected each scars and scars were harvested 1 week, 2 weeks, 4 weeks later. The wounds were stained with hematoxylin and eosin, TUNEL stain, immunohistochemical stain for VEGF and calculated scar elevation index. Results: Histologic analaysis demonstrated significant reduction in inflammation, vascularity and improvement in dermal collagen organization in experimental group. In TUNEL staining apotosis positive cells were increased and immunohistochemial staining of VEGF demonstrated significant reduction of VEGF expression in experimental group. No significant difference was noted in scar elevation index between two groups. Conclusion: This study suggest that intralesional injection of verapamil on early wound scarring of the rabbit ear decreased VEGF production and increased apoptosis and have a benefit on the pathophysiology of scar formation.
Keywords
scar; verapamil; apoptosis; VEGF;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Lee RC, Doong H, Jellema AF: The response of burn scars to intralesional verapamil. report of five cases, Arch Surg 129: 107, 1994   DOI   ScienceOn
2 Porter RA, Brown RA, Eastwood M, Occleston NL, Khaw PT: Ultrastructural changes during contraction of collagen lattices by ocular fibroblasts. Wound Repair Regen 6: 157, 1998   DOI   ScienceOn
3 Yao R, Cooper GM: Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267: 2003, 1995   DOI   PUBMED
4 Lee RC, Ping JA: Calcium antagonists retard extracellular matrix production in connective tissue equivalent. J Surg Res 49: 463, 1990   DOI   ScienceOn
5 D'Andrea F, Brongo S, Ferraro G, Baroni A: Prevention and treatment of keloids with intralesional verapamil. Dermatology 204: 60, 2002   DOI   ScienceOn
6 Kim YO, Kim SM, Jo NH, Nam TS: The effect of simultaneous steroid and verapamil injection on scar formation in the incisional wound of rat. J Korean Soc Plast Reconstr Surg 31: 375, 2004
7 Morris DE, Wu L, Zhao LL, Bolton L, Roth SI, Ladin DA, Mustoe TA: Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg 100: 674, 1997   DOI   ScienceOn
8 Sayah DN, Soo C, Shaw WW, Watson J, Messadi D, Longaker MT, Zhang X, Ting K: Downregulation of apoptosis-related genes in keloid tissues, J Surg Res 87: 209, 1999
9 Steinbrech DS, Mehrara BJ, Chau D, Rowe NM, Chin G, Lee T, Saadeh PB, Gittes GK, Longaker MT: Hypoxia upregulates VEGF production in keloid fibroblasts, Ann Plast Surg 42: 519, 1999
10 Giugliano G, Pasquali D, Notaro A, Brongo S, Nicoletti G, D'Andrea F, Bellastella A, Sinisi AA: Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts. Br J Plast Surg 56: 804, 2003   DOI   ScienceOn
11 Frank S, Stallmeyer B, Kampfer H, Kolb N, Pfeilschifter J: Nitric oxide triggers enhanced induction of vascular endothelial growth factor expression in cultured keratinocytes(HaCaT) and during cutaneous wound repair. FASEB J 13: 2002, 1999   DOI
12 Desmouliere A, Redard M, Darby I, Gabbiani G: Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J pathol 146: 56, 1995
13 Ladin DA, Hou Z, Patel D, McPhail M, Olson JC, Saed GM, Fivenson DP: p53 and apoptosis alterations in keloids and keloid fibroblasts. Wound Repair Regen 6: 28, 1998   DOI   ScienceOn
14 ira AK, Brown LF, Washington CV, Cohen C, Arbiser JL: Keloids demonstrate high-level epidermal expression of vascular endothelial growth factor, J Am Acad Dermatol 50: 850, 2004
15 Dang CM, Beanes SR, Lee H, Zhang X, Soo C, Ting K: Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio. Plast Reconstr Surg 111: 2273, 2003   DOI   ScienceOn