title: Vascular endothelium has a local anti-adenovirus vector system and glucocorticoid optimizes its gene transduction.
abstract: OBJECTIVE
  Although adenovirus is a powerful tool for vascular research and therapy, endothelial impairment after infection has been reported. We investigated the mechanisms of this impairment and the effect of dexamethasone (DEX) on gene transfer into the vascular endothelial cells.
  
  
  RESULTS
  Beta-galactosidase gene encoding adenovirus vector (beta-gal-Ad) (7.5 x 10(8) plaque-forming units/mL) transduced beta-gal into the rabbit organ-cultured pulmonary endothelium, followed by an apoptosis and an impairment of endothelium-dependent relaxation (EDR). Endothelial cell infected by beta-gal-Ad expressed proinflammatory genes mRNAs and suppressed endothelial nitric oxide synthase (eNOS) mRNA. Treatment with DEX dramatically increased beta-gal protein expression in the endothelium, attenuated beta-gal-Ad-induced apoptosis, and prevented the impairment of EDR. DEX also suppressed the mRNAs expressions of proinflammatory genes and recovered eNOS mRNA expression in organ-cultured vascular endothelium. In addition, we confirmed the DEX's beneficial effects in an endothelial cell line (in vitro) and rat femoral artery (in vivo) experiments.
  
  
  CONCLUSIONS
  These results suggest that adenovirus vector induces host-immune responses and apoptosis in vascular endothelial cells. DEX is found to be a useful and potent tool to prevent the Ad-induced impairments of the endothelium and to optimize gene expression efficiency by adenovirus vector at the protein translation level in both in vitro and in vivo experiments.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Sheng
authors.initials: S
authors.lastname: Lee
authors.forename: Akio
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kohama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Karaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D003360:Cosmids / Q000493:pharmacokinetics; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D005263:Femoral Artery / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011817:Rabbits; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes / Q000187:drug effects / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology / Q000821:virology*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D003907:Dexamethasone; D016572:Cyclosporine; D001616:beta-Galactosidase