title: Helper-dependent adenovirus is superior to first-generation adenovirus for expressing transgenes in atherosclerosis-prone arteries.
abstract: OBJECTIVE
  Vascular gene transfer is a powerful tool for investigating and treating vascular diseases; however, its utility is limited by brevity of transgene expression and vector-associated inflammation. Helper-dependent adenovirus (HDAd), an advanced-generation adenovirus that lacks all viral genes, is superior to first-generation adenovirus (FGAd) in normal rabbit arteries. We compared HDAd to FGAd in arteries of cholesterol-fed rabbits, a model of early atherogenesis in which transgene expression might be decreased, and inflammation increased.
  
  
  RESULTS
  Carotid arteries of chow- and cholesterol-fed rabbits were infused with FGAd, HDAd, or medium. HDAd expressed a transgene at least as well in arteries of cholesterol-fed rabbits as in arteries of chow-fed rabbits and expressed more durably than FGAd. In arteries of cholesterol-fed rabbits, HDAd stimulated less intimal growth, lipid deposition, and inflammation than FGAd. Neither vector affected phenylephrine-induced contraction or nitroprusside-mediated relaxation; however, both vectors decreased maximal acetylcholine-stimulated vasorelaxation. The relative absence of intimal growth in HDAd arteries could interfere with the utility of this model for testing atheroprotective genes; however, both coinfusion of FGAd and extension of cholesterol feeding yielded larger intimal lesions, on which atheroprotective genes could be tested.
  
  
  CONCLUSIONS
  HDAd is superior to FGAd for expression of transgenes in atherosclerosis-prone arteries.
authors: Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195-7710, USA.
authors: Bo
authors: B
authors: Jiang
authors: Kun
authors: K
authors: Qian
authors: Liang
authors: L
authors: Du
authors: Ian
authors: I
authors: Luttrell
authors: Kanchan
authors: K
authors: Chitaley
authors: David A
authors: DA
authors: Dichek
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology*; D006378:Helper Viruses / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D050356:Lipid Metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D011817:Rabbits; D019076:Transgenes; D017539:Tunica Intima / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1