title: Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery.
abstract: OBJECTIVE
  New and efficient strategies to protect endothelium or to enhance endothelial regrowth are important for treatment of restenosis after percutaneous transluminal angioplasty. Magnetic DNA microspheres are used to accelerate vascular endothelial growth factor (VEGF) re-endothelialization and to attenuate intimal hyperplasia in balloon-injured artery. This study aimed to assess DNA-gelatin magnetic nanospheres containing VEGF expression plasmids in vascular restenosis attenuation.
  
  
  METHODS
  Ninety-six rabbits underwent balloon injury and were randomly divided for gene transfer with naked VEGF plasmids (NAK group), magnetic VEGF microspheres (MIC group), and LacZ (CON group: naked LacZ plasmid and LacZ nanosphere subgroups). Serum and tissue VEGF levels were measured. Also, the ratios of intima area to media area were determined to assess neointima formation.
  
  
  RESULTS
  Microsphere gene delivery through the artery by a magnet resulted in VEGF overexpression in transfected arterial segments. Tissue VEGF integral optical densities were significantly increased in MIC rabbits compared with NAK animals. Serum VEGF was below detection in all animals. X-Gal staining showed higher transfection efficiency in the CON group. The impact of neointimal thickening was evaluated by light microscopy as the ratio of intima area to media area in cross sections. Significant differences in the ratio of intima area to media area were obtained between the NAK group (0.12 ± 0.02, 0.41 ± 0.03, 0.61 ± 0.05, and 0.72 ± 0.04 at 1, 2, 3, and 4 weeks, respectively) and the MIC group (0.06 ± 0.03, 0.20 ± 0.05, 0.25 ± 0.04, and 0.26 ± 0.03 at 1, 2, 3, and 4 weeks, respectively) at 2, 3, and 4 weeks (P < .05).
  
  
  CONCLUSIONS
  Intra-arterial VEGF gene delivery by magnetic microspheres significantly increased DNA stability, transfection efficiency, and targeting specificity, resulting in exogenous VEGF overexpression and attenuated intimal hyperplasia in balloon-injured artery.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang Province, China. Electronic address: tiemingzhangmedsci@163.com.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Qu
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D006965:Hyperplasia; D008280:Magnetics / Q000295:instrumentation; D058185:Magnetite Nanoparticles; D059346:Magnets; D008297:Male; D058426:Neointima; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D013997:Time Factors; D014162:Transfection / Q000295:instrumentation / Q000379:methods*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D058185:Magnetite Nanoparticles; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A