RESUMO
Gene transfer to the vessel wall using vascular endothelial growth factors (VEGFs) has shown therapeutic potential for the treatment of restenosis. In this study, we evaluated the effect of catheter-mediated adenoviral (Ad) gene transfer of the mature form of VEGF-D (VEGF-D(DeltaNDeltaC)) in balloon-denuded cholesterol-fed rabbit aorta. AdLacZ was used as a control. Transduced VEGF-D(DeltaNDeltaC) mRNA was detectable in the arterial wall with RT-PCR at 6, 14 and 28 days. Gene transfer efficiency as detected with X-gal staining 6 days after the AdLacZ transduction was 1.91 +/- 1.32% in intima. AdVEGF-D(DeltaNDeltaC) gene transfer led to 52% reduction in intima/media ratio (I/M) as compared to the AdLacZ controls at 14 days time point. At 6 days there were no differences in I/M, but the number of macrophages in the vessel wall was 85% lower in the AdVEGF-D(DeltaNDeltaC) group as compared to the controls. The therapeutic effect was no longer detectable 28 days after the gene transfer. The therapeutic effect of VEGF-D(DeltaNDeltaC) was nitric oxide (NO)-dependent as the feeding of NO synthase inhibitor, L-NAME, blocked the reduction in intimal thickening. It is concluded that AdVEGF-D(DeltaNDeltaC) gene transfer reduces intimal thickening and macrophage influx into the vessel wall in balloon-denuded rabbit aortas.
Assuntos
Adenoviridae/genética , Doenças da Aorta/terapia , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Transdução Genética/métodos , Fator D de Crescimento do Endotélio Vascular/genética , Animais , Aorta , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Cateterismo , Constrição Patológica/terapia , Neovascularização Patológica , Óxido Nítrico/metabolismo , Coelhos , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Fator D de Crescimento do Endotélio Vascular/metabolismoRESUMO
This study was performed to evaluate angiogenic responses of angiopoietin-1 (Ang1) in vivo after adenovirus-mediated gene transfer in the periadventitial space of the rabbit carotid arteries using a collar technique. Adenoviruses encoding LacZ and vascular endothelial growth factor (VEGF) receptor-1-Ig fusion protein (VEGF-R1-Ig) adenoviruses were used as controls. Increased neovessel formation was seen in adventitia of the Ang1 transduced arteries 7 days after the gene transfer. Neovessels in the Ang1 transduced arteries were large in size and well perfused. Ang1 binds to Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domain) receptors, which were expressed in the endothelium of the neovessels. When VEGF-R1-Ig was used with Ang1, it resulted in a decrease in the number of neovessels, which implies that VEGF-A or some other VEGF-R1 ligand(s) play a crucial role in angiogenesis occurring in response to Ang1. There were no significant differences in the total number of capillaries in the adventitia of the VEGF-R1-Ig transduced arteries as compared to LacZ controls. Neointima formation was not increased in the Ang1 transduced arteries as compared to the controls. We conclude that in the periadventitial space Ang1 shows angiogenic activity and is a potentially useful factor for the induction of therapeutic vascular growth in vivo.
Assuntos
Angiopoietina-1/genética , Artérias Carótidas , Terapia Genética/métodos , Neovascularização Fisiológica , Transdução Genética/métodos , Adenoviridae/genética , Animais , Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/uso terapêutico , Imunoglobulinas/genética , Injeções , Coelhos , Receptor TIE-2/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Transgenes , Túnica Íntima/fisiologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
The objective of this study was to determine the effectiveness of biopsychosocial rehabilitation for upper-limb repetitive-strain injuries among working-age adults. Studies were identified from electronic bibliographic databases, reference checks, and consultations with experts in rehabilitation. Four blinded reviewers selected randomized controlled and controlled trials. Two experts evaluated the clinical relevance of the findings. Two other reviewers extracted the data and assessed the main results and the methodological quality of the studies. Finally, a qualitative analysis was performed. Only 2 studies satisfied the criteria. They were both considered to be low-quality trials. The clinical relevance of the included studies was also unsatisfactory. The level of scientific evidence was limited, showing that hypnosis as a supplement to comprehensive treatment can decrease the pain intensity of acute repetitive-strain injury in short follow-ups. There appears to be little scientific evidence for the effectiveness of biopsychosocial rehabilitation with respect to repetitive-strain injuries.
