Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats

Life Sciences
Can-Sheng ZhuDun-Jing Wang

Abstract

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.

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Citations

Jan 10, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bart J CrielaardGert Storm
Oct 5, 2012·Annals of Neurology·Jorge CorrealeMaría C Ysrraelit
Oct 4, 2014·Clinical Reviews in Allergy & Immunology·Shang-An ShuPatrick S C Leung
Sep 18, 2012·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Jang-Mi ParkMun-Yong Lee
Apr 4, 2009·Physiological Reviews·Carmen Ruiz de AlmodovarPeter Carmeliet

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