title: Abnormal regulation of neo-vascularisation in deep partial thickness scalds in rats with diabetes mellitus.
abstract: OBJECTIVE
  This study observed the degree of neo-vascularisation and differential expression of angiogenesis growth factors and their receptor in deep partial-thickness scald wound with diabetes mellitus.
  
  
  METHODS
  Sixty Sprague-Dawley rats were randomised into a control group and an STZ-induced diabetic group, inflicted with partial-thickness scalding of 20% total body surface area (20% TBSA) on the back. Wound specimens were harvested immediately after scald and on 1, 3, 7, 10, 14 and 21 post-scald days (PSDs) to observe histological changes, and wound healing rates were calculated. The degree of neo-vascularisation in wound (labelled with blue microsphere) and the quantity of vascular endothelial cells (labelled with red CD31) were also measured by double-labelling immunofluorescence. Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie-2, vascular endothelial growth factor (VEGF) and Flt-1 messenger RNA (mRNA) were analysed by real-time RT-PCR. Ang-1, Ang-2 and VEGF protein expressions were measured by Western blotting.
  
  
  RESULTS
  Wound healing was markedly impaired in diabetic rats. The diabetic rats show inhibited vascularity in the wound edge at every time point (the quantitation of vascularity was 60.0±3.0 in the control group and 12.0±1.4 in the diabetic group, p<0.01 on day 7). Although neo-vascularisation in the number of endothelial cells was not significantly different compared with the normal group, part of new vascular endothelial cells did not form the vascular function. After injury, expression of Ang-2 mRNA and protein were increased in both groups, and the normal group showed decreases on day 7, 14 and 21, whereas the diabetic group showed significant increases. Although the expression VEGF and its receptors before injury was higher than the normal group, the level at 1, 3 and 7 days after injury was significantly lower than that 14 days, and that at 21 days after injury was significantly higher than the normal group.
  
  
  CONCLUSIONS
  Vascular endothelial cells can proliferate actively in the diabetic wound with deep partial-thickness burns, but it is still poor in blood supply due to lack of functional capillaries. The mechanism may be related to sustained abnormal high expression of Ang-2 and down-regulated VEGF.
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. qiaoliang@yahoo.com
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.forename: Shu-Liang
authors.initials: SL
authors.lastname: Lu
authors.forename: Jiao-Yun
authors.initials: JY
authors.lastname: Dong
authors.forename: Fei
authors.initials: F
authors.lastname: Song
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1