Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats.
Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease. However, it remains unknown whether anti-VEGF modalities could serve as a potential treatment for such central nervous system (CNS) autoimmune diseases. We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3) (the first three extracellular domains of Flt-1, the hVEGF receptor-1). Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF-induced inflammatory cell infiltration in matrigel plugs. When given intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector significantly reduced disease severity compared to untreated rats. sFlt-1(1-3) gene transfer blocked VEGF and greatly reduced the number of cells that express VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.
Zhu
Can-Sheng
CS
Department of Neurology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, People's Republic of China.
Hu
Xue-Qiang
XQ
Xiong
Zhao-Jun
ZJ
Lu
Zheng-Qi
ZQ
Zhou
Guo-Yu
GY
Wang
Dun-Jing
DJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000502:physiology*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1