Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats.
BACKGROUND
Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels.


OBJECTIVE
The effect of exogenously administered leptin on the healing process of a full tissue burn wound model.


METHODS
Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody.


RESULTS
The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density between the seventh and the ninth postoperative day among different groups treated with leptin. All wounds from the control group, as well as those from animal groups treated with the combined injection of leptin and antileptin did not develop any new vessels.


CONCLUSIONS
Exogenous administration of recombinant leptin increases early tissue angiogenesis in the burn wound level of an experimental animal model.
Liapaki
Ioannis
I
Department of Plastic and Reconstructive Surgery, Hellenic Anticancer Institute, Saint Savvas Hospital, Athens, Greece.
Anagnostoulis
Stavros
S
Karayiannakis
Anastasios
A
Korkolis
Dimitris
D
Labropoulou
Maria
M
Matarasso
Alan
A
Simopoulos
Constantinos
C
D042501:Angiogenic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002058:Burns, Electric / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D042501:Angiogenic Proteins; D020738:Leptin