The Anti-Apoptotic Effect of Transgenic Akt1 Gene on Cultured New-Born Rats Cardiomyocytes Mediated by Ultrasound/Microbubbles Destruction

  • Dongye Li
  • Xueyou Jiang
  • Tongda Xu
  • Jiantao Song
  • Hong zhu
  • Yuanyuan Luo
Conference paper
Part of the Lecture Notes in Electrical Engineering book series (LNEE, volume 269)


The purpose of this study was to transfect exogenous Akt1 to 293FT cells and cultured new-born rats cardiomyocytes respectively for exploring the feasibility and safety of the new method. In addition, the protective effects on cultured cardiomyocytes suffering from ischemia/reperfusion injury (I/R inury) of the transgenic Akt1 gene mediated by ultrasound-induced microbubble destruction (US/MB) were also observed. 293FT cells and cardiomyocytes were divided into four groups, group A: only pEGFPC1- Akt1; group B: MB + pEGFPC1-Akt1; group C: US + pEGFPC1-Akt1; group D: US + MB + pEGFPC1-Akt1. The results showed that microbubble alone could not deliver exogenous genes to target cells without ultrasound, but the latter could without the help of microbubble, ultrasound with simultaneous microbubble could enhance the transfection rate significantly. Ultrasound frequency 1.7 MHz, mechanical index (MI) 1.5, irradiation time 2 min, MB volume concentration 15 %. According to the above ultrasound parameters, Akt1 gene was transfected to cultured cardiomyocytes and then allowed them to suffer from I/R injury, our results showed that the transgenic Akt1 gene was expressed and had significant anti-apoptotic effect. The results suggested that US/MB was a promising gene delivery system for gene therapy in heart diseases.


Ultrasound Microbubble Gene transfection Akt Cardiomyocyte 


  1. 1.
    Oliver JM, Hugo AK, Raffi B (2007) Targeting the heart with gene therapy-optimized gene delivery methods. Cardiovasc Res 73:453–462CrossRefGoogle Scholar
  2. 2.
    Isao K, Koji O, Akira O et al (2004) Using ultrasonic microbubble destruction transfer: the first demonstration of myocardial transfer of a “functional” gene. Treatment of acute myocardial infarction by hepatocyte growth factor gene. J Am Coll Cardiol 44:644–653CrossRefGoogle Scholar
  3. 3.
    Kulik G, Klippel A, Weber MJ (1997) Antiapoptotic signalling by the IGF-I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol 17:1595–1606Google Scholar
  4. 4.
    Takashi M, Jingzang T, Federica M et al (2001) Akt Activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104:330–335CrossRefGoogle Scholar
  5. 5.
    Sirsi SR, Borden MA (2012) Advances in ultrasound mediated gene therapy using microbubble contrast agents. Theranostics 2:1208–1222CrossRefGoogle Scholar
  6. 6.
    Price RJ, Kaul S (2002) Contrast ultrasound targeted drug and gene delivery: an update on a new therapeutic modality. J Cardiovasc Pharmacol Ther 73:171–180CrossRefGoogle Scholar
  7. 7.
    Staub D, Partovi S, Imfeld S et al (2013) Novel applications of contrast-enhanced ultrasound imaging in vascular medicine. Vasa 42:17–31CrossRefGoogle Scholar
  8. 8.
    Wan Xinghua, Liang Hai-Dong, Dong Baowei et al (2005) Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of mice: comparison between commercially available microbubble. Radiology 237:224–229CrossRefGoogle Scholar
  9. 9.
    Lawrie A, Brisken AF, Francis SE et al (1999) Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro. Circulation 99:2617–2620CrossRefGoogle Scholar
  10. 10.
    Unnikrishnan S, Klibanov AL (2012) Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application. Am J Roentgenol 199:292–299CrossRefGoogle Scholar
  11. 11.
    Fischer AJ, Stanke JJ, Omar G et al (2006) Ultrasound- mediated gene transfer into neuronal cells. J Biotechnol 122:393–411CrossRefGoogle Scholar
  12. 12.
    Zheng MM, Zhou XY, Wang LP et al (2012) Experimental research of RB94 gene transfection into retinoblastoma cells using ultrasound-targeted microbubble destruction. Ultrasound Med Biol 38:1058–1066CrossRefGoogle Scholar
  13. 13.
    Derek JH, Mihaela MM, Derek MY (2004) Cross-talk between the survival kinases during early reperfusion: its contribution to ischemic preconditioning. Cardiovasc Res 63:305–312CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Dongye Li
    • 1
  • Xueyou Jiang
    • 2
  • Tongda Xu
    • 1
  • Jiantao Song
    • 3
  • Hong zhu
    • 1
  • Yuanyuan Luo
    • 1
  1. 1.Department of CardiologyInstitute of Cardiovascular Diseases, the Affiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  2. 2.Department of Cardiology of Second Hospital of NanJingNanjingChina
  3. 3.Department of Cardiology, the Affiliated Hospital of Shandong Medical UniversityJi-nanChina

Personalised recommendations