Ann Dermatol.  2008 Jun;20(2):49-55. 10.5021/ad.2008.20.2.49.

COMP-angiopoietin 1 Gene Transfer Enhances Cutaneous Wound Healing by Promoting Angiogenesis

Affiliations
  • 1Department of Dermatology, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Korea. yymmpark@hotmail.com
  • 2Gowoonsesang Dermatology Clinic, Korea.
  • 3Department of Neurology, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Biological Sciences, Biomedical Center, Korea Advanced Institute of Science and Technology, Daejeon, Korea.

Abstract

BACKGROUND: Angiogenesis is crucial for wound healing and exogenous supplements of the angiogenic growth factors have been known to promote cutaneous wound healing. Angiopoietin (Ang) 1 is a recently discovered angiogenic factor and there have been few studies of its effect on cutaneous wound healing.
OBJECTIVE
We examined the effect of Ang 1 on cutaneous wound healing.
METHODS
Cartilage oligomeric matrix protein (COMP)-Ang 1 (Ade-COMP-Ang 1)- was intravenously injected to rats two days before surgery creating full-thickness wounds. The clinical wound healing rate and the number of vessels in the skin samples were evaluated on days 3, 7 and 14 post operation.
RESULTS
At post-operation day 3, 7 and 14, the clinical wound healing rate was 38.3%, 59.4% and 92.1%, respectively, in the Ade-COMP-Ang 1-treated group, compared with 20.5%, 47.5% and 87.3%, respectively, in the Ade-LacZ-treated group. There were significant differences in the results of day 3 and day 7 between two groups (p<0.05). Histopathologically, the number of the vessels of the Ade-COMP-Ang 1-treated group was 73.7, 94.1 and 62.7 at day 3, 7 and 14, compared with that of the Ade-LacZ-treated group, 53.5, 83.9, and 56.9. The differences in the results of the two groups were statistically significant (p<0.05).
CONCLUSION
These results indicate that Ade-COMP-Ang 1 therapy significantly accelerats wound healing by promoting angiogenesis. However, further study using Ade-COMP-Ang 1 gene therapy for chronic wounds in which the formation of new blood vessels is impaired is needed in the near future.

Keyword

Angiogensis; COMP-angiopoietin 1; Cutaneous wound healing

MeSH Terms

Angiogenesis Inducing Agents
Animals
Blood Vessels
Cartilage
Extracellular Matrix Proteins
Genetic Therapy
Glycoproteins
Intercellular Signaling Peptides and Proteins
Rats
Skin
Wound Healing
Angiogenesis Inducing Agents
Extracellular Matrix Proteins
Glycoproteins
Intercellular Signaling Peptides and Proteins

Figure

  • Fig. 1 (A) The effect of Ade-COMP-Ang 1 on clinical wound healing. The treatment of Ade-COMP-Ang 1 showed 39.5%, 59.3% and 91.8% reduction of wound size at day 3, 7 and 14, compared with 20.4%, 46.2% and 89.0%, in the Ade-LacZ treated group, respectively. The results of day 3 and 7 between the Ade-COMP-Ang 1 treated group and the Ade-LacZ treated group were statistically significant (*p<0.05). (B) A representative example of the cutaneous wound healing of the Ade-COMP-Ang 1-treated and Ade-LacZ treated groups at day 0, 3, 7 and 14. The wound healing rate was accelerated in the Ade-COMP-Ang 1-treated group, compared with Ade-LacZ-treated group. Ade-LacZ-treated group: a (day 0), b (day 3), c (day 7), d (day 14 after wound surgery), Ade-COMP-Ang 1-treated group: e (day 0), f (day 3), g (day 7), h (day 14 after wound surgery).

  • Fig. 2 (A) The effect of Ade-COMP-Ang 1 on angiogenesis. Under the high power field view (×200), the number of blood vessels of the Ade-COMP-Ang 1-treated group was 73.7, 94.1 and 62.7 at day 3, 7 and 14, respectively, compared with that of the Ade-LacZ treated group, i.e., 53.5, 83.9, and 56.9, respectively. The results of day 3, 7 and 14 between the Ade-COMP-Ang 1 treated group and the Ade-LacZ treated group were statistically significant (*p<0.05). (B) The blood vessel formation of the Ade-COMP-Ang 1 treated and Ade-LacZ treated groups at day 3, 7 and 14 (PECAM, ×200). The number of blood vessels were increased in the the Ade-COMP-Ang 1-treated group, compared with Ade-LacZ-treated group. Ade-LacZ-treated group: a (day 3), c (day 7), e (day 14 after wound surgery), Ade-COMP-Ang 1-treated group: b (day 3), d (day 7), f (day 14 after wound surgery).


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