BioMed Research International (2017-01-01)

Enhancement of Angiogenesis by Ultrasound-Targeted Microbubble Destruction Combined with Nuclear Localization Signaling Peptides in Canine Myocardial Infarction

  • Jingjing Cui,
  • Qing Deng,
  • Qing Zhou,
  • Sheng Cao,
  • Nan Jiang,
  • Yijia Wang,
  • Jinling Chen,
  • Bo Hu,
  • Tuantuan Tan

DOI
https://doi.org/10.1155/2017/9390565
Journal volume & issue
Vol. 2017

Abstract

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Objective. This study aimed to develop a gene delivery system using ultrasound-targeted microbubbles destruction (UTMD) combined with nuclear localization signal (NLS) and investigate its efficacy and safety for therapeutic angiogenesis in canine myocardial infarction (MI) model. Methods. Fifty MI dogs were randomly divided into 5 groups and transfected with Ang-1 gene plasmid: (i) group A: only injection of microbubbles and Ang-1 plasmid; (ii) group B: only UTMD mediated gene transfection; (iii) group C: UTMD combined with classical NLS mediated gene transfection; (iv) group D: UTMD combined with mutational NLS mediated transfection; and (v) group E: UTMD combined with classical NLS in the presence of a nucleus transport blocker. The mRNA and protein expression of Ang-1 gene, microvessel density (MVD) cardiac troponin I (cTnI), and cardiac function were determined after transfection. Results. The expression of mRNA and protein of Ang-1 gene in group C was significantly higher than that of the other groups (all P < 0.01). The MVD of group C was 10.2-fold of group A and 8.1-fold of group E (P < 0.01). The cardiac function in group C was significant improvement without cTnI rising. Conclusions. The gene delivery system composed of UTMD and NLS is efficient and safe.