RESUMEN
It has been previously shown that vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis during wound repair and that healing-impaired diabetic mice show decreased VEGF expression levels. In order to investigate the potential benefits of gene therapy with growth factors on wound repair, a replication-deficient recombinant adenovirus vector carrying the human VEGF(165) gene (AdCMV.VEGF(165)) was topically applied on excisional wounds of streptozotocin-induced diabetic mice. Treatment with AdCMV.VEGF(165) significantly accelerated wound closure when compared with AdCMV.LacZ-treated, as well as saline-treated control mice, by promoting angiogenesis at the site of injury. Our findings suggest that AdCMV.VEGF(165) may be regarded as a therapeutic tool for the treatment of diabetic ulcers.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Factores de Crecimiento Endotelial/fisiología , Terapia Genética/métodos , Linfocinas/fisiología , Neovascularización Fisiológica/fisiología , Piel/lesiones , Cicatrización de Heridas/fisiología , Adenoviridae/genética , Animales , Factores de Crecimiento Endotelial/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Tejido de Granulación/anatomía & histología , Linfocinas/genética , Masculino , Ratones , Piel/irrigación sanguínea , Transducción Genética , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Several chemokines, belonging to both the CXC and CC classes, act as positive or negative regulators of angiogenesis. We sought to investigate the role of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphocyte chemoattractant (BLC), on endothelial cell functions. We tested the effect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibroblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-induced functions, while is not active by itself. To test whether other FGF-2-mediated biological activities may be affected, we evaluated the ability of CXCL13 to rescue HUVEC from starvation-induced apoptosis, as FGF-2 is a survival factor for endothelial cells, and found that CXCL13 partially inhibits such rescue. Multiple mechanisms may be responsible for these biological activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhibits FGF-2 homodimerization, and induces the formation of CXCL13-FGF-2 heterodimers. Our data suggest that CXCL13 may modulate angiogenesis by interfering with FGF-2 activity.
