ISSN:
1524-475X
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Identifying molecular loci of impaired cutaneous healing in diabetes with an eye towards developing targeted therapy to ameliorate dysrepair continues to evolve as a promising area of study. By using an excisional wound model produced on the dorsum of female diabetic C57BL/KsJ db + /db+ mice as well as their normal (WT) & heterozygous (HZ) littermates, we studied the effects of peri-wound intradermal injection of adeno-associated viral vector (AAV) expressing the 165-amino acid isoform of human vascular endothelial growth factor (VEGF) on the following: kinetics of re-epithelialization, neoangiogenesis and granulation tissue formation, matrix remodelling, collagen deposition, and maturation. One sq. in. full thickness excisional wound was created in the mid-upper back, rendering half of the wound as either right or left paravertebral. Animals were randomized to receive 1 of 3 treatments via intradermal injection: 1)VEGF (AAV) vector; 2)Adnull vector; 3)PBS. Postoperatively, wounds were examined & photographed on Days 3, 7, 10, 14, 21 & 28. Also, tissue was harvested for histology & immunohistochemistry (PECAM), and snap frozen for protein & RNA analysis. A scoring system was used to grade re-epithelialization, granulation tissue thickness, matrix density, inflammation, vascular density, epithelial maturity. AAV-VEGF exerted minimal effect on repair in WT and HZ mice. However, pronounced neovascularization, thickened granulation tissue & increased matrix deposition was noted after VEGF treatment in the db/db mice compared to those that received PBS or adnull vector at all timepoints. While the induction of angiogenesis in VEGF treated db/db mice lagged behind the unimpaired mice by 5–7 days, a global improvement in wound healng was observed.R Crystal, Dir Inst Genetic Medicine, Weill Med College-Cornell Univ
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1067-1927.2004.0abstractz.x
