Recombinant human endostatin reduces hypertrophic scar formation in rabbit  ear model through down- regulation of VEGF and TIMP-1.

Peng Wang, Li-Zhu Jiang, Bin Xue
1. Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing,
China; wangpeng.2015@hotmail.com
2. Department of Otolaryngology, First Affiliated Hospital of Chongqing Medical University, Chongqing,
China; pearl1984@sina.com
3. Department of Burn and Plastic Surgery, First Affiliated Hospital of Chongqing Medical University,
Chongqing, China; CQXuebin@126.com

Abstract
Background: Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. Hypertrophic scar (HS) tissue, much like a carcinoma, is often associated with angiogenesis. However, there have been few studies conducted on the effects of Endostar on HS or its mechanism.

Objective:This paper investigated the effects Endostar on the HS of rabbit ears and studied the effects of Endostar on VEGF
and TIMP-1 expression.

Methods:Sixteen New Zealand white rabbits were used to establish HS models. Then, rabbit ears containing HS were randomly  assigned to either the Endostar group or the control group. The changes of appearance and histology were evaluated using the  naked eye, hematoxylin eosin staining, and a scar elevation index. The VEGF and TIMP-1 expressions were detected by immunohistochemical staining, RT-PCR, and western blot.

Results: The thickness of the connective tissue in the Endostar group were thinner, the numbers of micro vessels and fibroblasts were fewer, and the collagen fibers were smoother. Moreover, the mRNA and protein expressions of VEGF and TIMP-1  in the Endostar group were significantly lower than those in the control group.

Conclusion:The results suggested that Endostar reduced the formation of HS by down-regulation of VEGF and TIMP-1
expressions.

Keywords: Endostar, endostatin, hypertrophic scar, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1