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Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method.

Publication ,  Journal Article
Aoki, M; Morishita, R; Muraishi, A; Moriguchi, A; Sugimoto, T; Maeda, K; Dzau, VJ; Kaneda, Y; Higaki, J; Ogihara, T
Published in: J Mol Cell Cardiol
March 1997

The lack of efficient treatment for myocardial infarction remains an unresolved problem in the field of cardiovascular disease. Gene therapy may be a potential therapeutic strategy for the treatment of myocardial infarction. However, current methods of in vivo gene transfer into the heart are limited by their low efficiency and/or potential toxicity. In the present study, we developed an efficient technique of gene transfer into the intact heart in vivo using the Sendai virus (HVJ: Hemagglutinating Virus of Japan)--liposome method. We used the beta-galactosidase gene, luciferase gene and human angiotensin converting enzyme (ACE) gene as markers. In vivo gene transfer into the rat heart was performed as follows: (1) direct injection into the rat heart, (2) incubation within the pericardium, and (3) infusion into a coronary artery. Direct injection of the HVJ-liposome complex containing the beta-galactosidase vector into the rat heart resulted in limited staining of beta-galactosidase 3 days after transfection. To compare transfection efficiency between "naked" plasmid DNA transfection and the HVJ-liposome method, we also transfected the luciferase reporter gene into the heart. Luciferase activity was significantly higher in hearts transfected by the HVJ-liposome method than that in hearts transfected by direct "naked" plasmid transfection (P < 0.01). To confirm the successful gene in the protein level, we measured ACE activity in the hearts. Cardiac ACE activity was significantly increased in hearts transfected with human ACE gene as compared to hearts transfected with control vector (P < 0.01). On the other hand, incubation of HVJ-liposome complex, containing beta-galactosidase vector, within the pericardium resulted in widespread staining of cardiac myocytes and fibroblasts, mainly located in several surface layers beneath the pericardium. More importantly, widespread stained areas of beta-galactosidase were also observed in the middle of the myocardium around the vasa vasorum. We also examined the efficiency of gene transfer by the HVJ-liposome method in a rat myocardial infarction model. In the infarction model, using the pericardium incubation approach, staining for beta-galactosidase was observed in the viable cells around the infarction area. Finally, direct infusion of the HVJ complex, containing the beta-galactosidase vector, into coronary artery also resulted in widespread staining of beta-galactosidase in cardiac myocytes around the microvasculature. Using direct injection, we found significant injury to the myocardium and severe fibrosis at the injection site, whereas no apparent injury was observed using pericardium incubation and coronary infusion. There was no evidence of cytotoxicity or inflammation caused by the HVJ-liposome complex itself. Overall, we have established an efficient in vivo gene transfer method into the heart using the HVJ-liposome method. Direct infusion into the coronary artery resulted in widespread transfection without damaging the myocytes; incubation within the pericardium demonstrated the usefulness of the HVJ-liposome method for studying cardiac function and as a means of gene therapy for cardiovascular diseases.

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Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

March 1997

Volume

29

Issue

3

Start / End Page

949 / 959

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Respirovirus
  • Rats, Sprague-Dawley
  • Rats
  • Plasmids
  • Pericardium
  • Peptidyl-Dipeptidase A
  • Myocardium
  • Myocardial Infarction
  • Luciferases
 

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Aoki, M., Morishita, R., Muraishi, A., Moriguchi, A., Sugimoto, T., Maeda, K., … Ogihara, T. (1997). Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method. J Mol Cell Cardiol, 29(3), 949–959. https://doi.org/10.1006/jmcc.1996.0337
Aoki, M., R. Morishita, A. Muraishi, A. Moriguchi, T. Sugimoto, K. Maeda, V. J. Dzau, Y. Kaneda, J. Higaki, and T. Ogihara. “Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method.J Mol Cell Cardiol 29, no. 3 (March 1997): 949–59. https://doi.org/10.1006/jmcc.1996.0337.
Aoki M, Morishita R, Muraishi A, Moriguchi A, Sugimoto T, Maeda K, et al. Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method. J Mol Cell Cardiol. 1997 Mar;29(3):949–59.
Aoki, M., et al. “Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method.J Mol Cell Cardiol, vol. 29, no. 3, Mar. 1997, pp. 949–59. Pubmed, doi:10.1006/jmcc.1996.0337.
Aoki M, Morishita R, Muraishi A, Moriguchi A, Sugimoto T, Maeda K, Dzau VJ, Kaneda Y, Higaki J, Ogihara T. Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method. J Mol Cell Cardiol. 1997 Mar;29(3):949–959.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

March 1997

Volume

29

Issue

3

Start / End Page

949 / 959

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Respirovirus
  • Rats, Sprague-Dawley
  • Rats
  • Plasmids
  • Pericardium
  • Peptidyl-Dipeptidase A
  • Myocardium
  • Myocardial Infarction
  • Luciferases