Combined gene therapy with vascular endothelial growth factor plus apelin in a chronic cerebral hypoperfusion model in rats
| Autor: | Shingo Nishihiro, Nobuyuki Takakura, Isao Date, Hiroyasu Kidoya, Tomohito Hishikawa, Tomohisa Shimizu, Yuji Takasugi, Kenji Sugiu, Yukei Shinji, Jun Haruma, Masafumi Hiramatsu, Koji Tokunaga |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine medicine.medical_specialty Angiogenesis medicine.medical_treatment Genetic enhancement Revascularization Brain Ischemia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Rats Wistar Receptor business.industry Genetic Therapy General Medicine Combined Modality Therapy Rats Cortex (botany) Apelin Vascular endothelial growth factor Disease Models Animal 030104 developmental biology Endocrinology chemistry Chronic Disease Moyamoya Disease Ligation business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurosurgery. 127:679-686 |
| ISSN: | 1933-0693 0022-3085 |
| DOI: | 10.3171/2016.8.jns16366 |
| Popis: | OBJECTIVEThe aim of this study was to evaluate whether combined gene therapy with vascular endothelial growth factor (VEGF) plus apelin during indirect vasoreconstructive surgery enhances brain angiogenesis in a chronic cerebral hypoperfusion model in rats.METHODSA chronic cerebral hypoperfusion model induced by the permanent ligation of bilateral common carotid arteries (CCAs; a procedure herein referred to as “CCA occlusion” [CCAO]) in rats was employed in this study. Seven days after the CCAO procedure, the authors performed encephalo-myo-synangiosis (EMS) and injected plasmid(s) into each rat's temporal muscle. Rats were divided into 4 groups based on which plasmid was received (i.e., LacZ group, VEGF group, apelin group, and VEGF+apelin group). Protein levels in the cortex and attached muscle were assessed with enzyme-linked immunosorbent assay (ELISA) on Day 7 after EMS, while immunofluorescent analysis of cortical vessels was performed on Day 14 after EMS.RESULTSThe total number of blood vessels in the cortex on Day 14 after EMS was significantly larger in the VEGF group and the VEGF+apelin group than in the LacZ group (p < 0.05, respectively). Larger vessels appeared in the VEGF+apelin group than in the other groups (p < 0.05, respectively). Apelin protein on Day 7 after EMS was not detected in the cortex for any of the groups. In the attached muscle, apelin protein was detected only in the apelin group and the VEGF+apelin group. Immunofluorescent analysis revealed that apelin and its receptor, APJ, were expressed on endothelial cells (ECs) 7 days after the CCAO.CONCLUSIONSCombined gene therapy (VEGF plus apelin) during EMS in a chronic cerebral hypoperfusion model can enhance angiogenesis in rats. This treatment has the potential to be a feasible option in a clinical setting for patients with moyamoya disease. |
| Databáze: | OpenAIRE |
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