Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Apr 1;99(7):1645–1650. doi: 10.1172/JCI119327

In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.

K Suzuki 1, Y Sawa 1, Y Kaneda 1, H Ichikawa 1, R Shirakura 1, H Matsuda 1
PMCID: PMC507984  PMID: 9120008

Abstract

Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.

Full Text

The Full Text of this article is available as a PDF (316.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ang D., Liberek K., Skowyra D., Zylicz M., Georgopoulos C. Biological role and regulation of the universally conserved heat shock proteins. J Biol Chem. 1991 Dec 25;266(36):24233–24236. [PubMed] [Google Scholar]
  2. Ardehali A., Fyfe A., Laks H., Drinkwater D. C., Jr, Qiao J. H., Lusis A. J. Direct gene transfer into donor hearts at the time of harvest. J Thorac Cardiovasc Surg. 1995 Apr;109(4):716–720. doi: 10.1016/S0022-5223(95)70353-5. [DOI] [PubMed] [Google Scholar]
  3. Black S. C., Lucchesi B. R. Heat shock proteins and the ischemic heart. An endogenous protective mechanism. Circulation. 1993 Mar;87(3):1048–1051. doi: 10.1161/01.cir.87.3.1048. [DOI] [PubMed] [Google Scholar]
  4. Currie R. W. Effects of ischemia and perfusion temperature on the synthesis of stress-induced (heat shock) proteins in isolated and perfused rat hearts. J Mol Cell Cardiol. 1987 Aug;19(8):795–808. doi: 10.1016/s0022-2828(87)80390-5. [DOI] [PubMed] [Google Scholar]
  5. Currie R. W., Tanguay R. M. Analysis of RNA for transcripts for catalase and SP71 in rat hearts after in vivo hyperthermia. Biochem Cell Biol. 1991 May-Jun;69(5-6):375–382. doi: 10.1139/o91-057. [DOI] [PubMed] [Google Scholar]
  6. Currie R. W., Tanguay R. M., Kingma J. G., Jr Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts. Circulation. 1993 Mar;87(3):963–971. doi: 10.1161/01.cir.87.3.963. [DOI] [PubMed] [Google Scholar]
  7. French B. A., Mazur W., Geske R. S., Bolli R. Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation. 1994 Nov;90(5):2414–2424. doi: 10.1161/01.cir.90.5.2414. [DOI] [PubMed] [Google Scholar]
  8. Heads R. J., Latchman D. S., Yellon D. M. Stable high level expression of a transfected human HSP70 gene protects a heart-derived muscle cell line against thermal stress. J Mol Cell Cardiol. 1994 Jun;26(6):695–699. doi: 10.1006/jmcc.1994.1084. [DOI] [PubMed] [Google Scholar]
  9. Huber S. A. Heat-shock protein induction in adriamycin and picornavirus-infected cardiocytes. Lab Invest. 1992 Aug;67(2):218–224. [PubMed] [Google Scholar]
  10. Hutter M. M., Sievers R. E., Barbosa V., Wolfe C. L. Heat-shock protein induction in rat hearts. A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection. Circulation. 1994 Jan;89(1):355–360. doi: 10.1161/01.cir.89.1.355. [DOI] [PubMed] [Google Scholar]
  11. Isaka Y., Fujiwara Y., Ueda N., Kaneda Y., Kamada T., Imai E. Glomerulosclerosis induced by in vivo transfection of transforming growth factor-beta or platelet-derived growth factor gene into the rat kidney. J Clin Invest. 1993 Dec;92(6):2597–2601. doi: 10.1172/JCI116874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kaneda Y., Iwai K., Uchida T. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science. 1989 Jan 20;243(4889):375–378. doi: 10.1126/science.2911748. [DOI] [PubMed] [Google Scholar]
  13. Knowlton A. A., Brecher P., Apstein C. S. Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest. 1991 Jan;87(1):139–147. doi: 10.1172/JCI114963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Li G. C., Li L. G., Liu Y. K., Mak J. Y., Chen L. L., Lee W. M. Thermal response of rat fibroblasts stably transfected with the human 70-kDa heat shock protein-encoding gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1681–1685. doi: 10.1073/pnas.88.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lin H., Parmacek M. S., Morle G., Bolling S., Leiden J. M. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation. 1990 Dec;82(6):2217–2221. doi: 10.1161/01.cir.82.6.2217. [DOI] [PubMed] [Google Scholar]
  16. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  17. Marber M. S., Latchman D. S., Walker J. M., Yellon D. M. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation. 1993 Sep;88(3):1264–1272. doi: 10.1161/01.cir.88.3.1264. [DOI] [PubMed] [Google Scholar]
  18. Marber M. S., Mestril R., Chi S. H., Sayen M. R., Yellon D. M., Dillmann W. H. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest. 1995 Apr;95(4):1446–1456. doi: 10.1172/JCI117815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mestril R., Chi S. H., Sayen M. R., O'Reilly K., Dillmann W. H. Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury. J Clin Invest. 1994 Feb;93(2):759–767. doi: 10.1172/JCI117030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morishita R., Gibbons G. H., Ellison K. E., Nakajima M., Zhang L., Kaneda Y., Ogihara T., Dzau V. J. Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8474–8478. doi: 10.1073/pnas.90.18.8474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakamura N., Horibe S., Matsumoto N., Tomita T., Natsuume T., Kaneda Y., Shino K., Ochi T. Transient introduction of a foreign gene into healing rat patellar ligament. J Clin Invest. 1996 Jan 1;97(1):226–231. doi: 10.1172/JCI118395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ono K., Lindsey E. S. Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg. 1969 Feb;57(2):225–229. [PubMed] [Google Scholar]
  23. Plumier J. C., Ross B. M., Currie R. W., Angelidis C. E., Kazlaris H., Kollias G., Pagoulatos G. N. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J Clin Invest. 1995 Apr;95(4):1854–1860. doi: 10.1172/JCI117865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stratford-Perricaudet L. D., Makeh I., Perricaudet M., Briand P. Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest. 1992 Aug;90(2):626–630. doi: 10.1172/JCI115902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Walker D. M., Pasini E., Kucukoglu S., Marber M. S., Iliodromitis E., Ferrari R., Yellon D. M. Heat stress limits infarct size in the isolated perfused rabbit heart. Cardiovasc Res. 1993 Jun;27(6):962–967. doi: 10.1093/cvr/27.6.962. [DOI] [PubMed] [Google Scholar]
  26. Wall S. R., Fliss H., Korecky B. Role of catalase in myocardial protection against ischemia in heat shocked rats. Mol Cell Biochem. 1993 Dec 22;129(2):187–194. doi: 10.1007/BF00926367. [DOI] [PubMed] [Google Scholar]
  27. Wu B., Hunt C., Morimoto R. Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol. 1985 Feb;5(2):330–341. doi: 10.1128/mcb.5.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yellon D. M., Latchman D. S. Stress proteins and myocardial protection. J Mol Cell Cardiol. 1992 Feb;24(2):113–124. doi: 10.1016/0022-2828(92)93148-d. [DOI] [PubMed] [Google Scholar]
  29. Yellon D. M., Pasini E., Cargnoni A., Marber M. S., Latchman D. S., Ferrari R. The protective role of heat stress in the ischaemic and reperfused rabbit myocardium. J Mol Cell Cardiol. 1992 Aug;24(8):895–907. doi: 10.1016/0022-2828(92)91102-b. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES