Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

Abstract

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. Purpose: 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. Conclusion: Exogenous administration of recombinant leptin increases early tissue angiogenesis in the burn wound level of an experimental animal model.

Severe burn and disuse in the rat independently adversely impact body composition and adipokines

“…In the present study, reduced adipokine levels were observed in the presence of injury rather than disuse, suggesting a greater influence of the injury component. Administration of leptin in burned rats has been shown to increase angiogenesis in injured tissues and decrease multiple organ damage [54,55]. Resistin was not altered in the present studies, but has been reported to be decreased in children with burns [56].…”

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

“…We also observed that ANGPT1 showed the statistically significant decrease in mRNA expression 1 day after the skin incisions. These factors have been reported to promote angiogenesis [6,[19][20][21]23,27,33,34], and their decreases may indicate that complex mechanisms may be involved in our skin wound system.…”

“…(CSF3/G-CSF) [11][12][13][14][15], chemokine (C-X-C motif) ligand2 (CXCL2) [16,17], chemokine (C-X-C motif) ligand 12 (CXCL12/SDF1) [18][19][20][21], endothelin 1 (ET1) [22], fibroblast growth factor 1 (FGF 1) [23], hepatocyte growth factor (HGF) [24,25], hypoxia inducible factor 1 alpha (HIF1a) [26], leptin [27], matrix metallopeptidase 9 (MMP9) [18,28,29], serpine/plasminogen activator inhibitor 1 (PAI1) [29][30][31], platelet-derived growth factor-A (PDGF-A) [18,32], transforming growth factor alpha (TGFa) [33,34], transforming growth factor beta 1 (TGFb1) [35,36], tenomodulin (TNMD) [37], and troponin I type 2 (TNNI2) [38,39]. Factors known to be involved in lymphangiogenesis such as fibroblast growth factor 2 (FGF 2) [40,41], c-fos induced growth factor (FIGF/VEGF-D) [42,43], forkhead box C 2 (FOXC2) [44][45][46], and prospero homeobox 1 (PROX1) [46][47][48][49] are also included in the study.…”

Signals from fat after injury: Plasma adipokines and ghrelin concentrations in the severely burned

“…The majority of these studies have focused on a single adipokine at a time in patients. Recently, in animal models of burns, significant alterations in adipokines have been reported, and interventions to attenuate these responses have been associated with improved outcomes [8-10]. Increasing evidence of alterations in adipokines in critically ill patients and promising interventional studies in animals have led to a rethinking of the role of adipose tissue in the care and outcome of the critically injured patient, with the possibility of novel therapeutic interventions.…”