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Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats

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Abstract

Apoptosis in the myocardium is linked to ischemia/reperfusion injury, and TNF-alpha induces apoptosis in cardiomyocytes. A significant amount of TNF-alpha is detected after ischemia and reperfusion. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNF-alpha receptor 1 and is an antagonist to TNF-alpha. In the present study, we examined the effects of sTNFR1 on infarct size in acute myocardial infarction (AMI) following ischemia/reperfusion. Male Wistar rats were subjected to left coronary artery (LCA) ligation. After 30 min of LCA occlusion, the temporary ligature on the LCA was released and blood flow was restored. Immediately after reperfusion, a total of 200 μg of sTNFR1 or LacZ plasmid was injected into three different sites of the left ventricular wall. At 6 h, 1 and 2 days after reperfusion, the TNF-alpha bioactivity in the myocardium was significantly higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase in the TNF-alpha bioactivity. The sTNFR1 plasmid significantly reduced DNA fragmentation and caspase activity compared to the LacZ plasmid. Finally, the sTNFR1 expression-plasmid treatment significantly reduced the area of myocardial infarction at 2 days after ischemia/reperfusion compared to LacZ plasmid. In conclusion, the TNF-alpha bioactivity in the heart increased from the early stage of ischemia/reperfusion, and this increase was thought to contribute in part to the increased area of myocardial infarction. Suppression of TNF-alpha bioactivity with the sTNFR1 plasmid reduced the infarct size in AMI following ischemia and reperfusion (Mol Cell Biochem 266: 127–132, 2004)

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References

  1. Stampfer MJ, Goldhaber SZ, Yusuf S, Petro R, Hennekens CH: Effect of intravenous streptokinase on acute myocardial infarction: pooled results from randomized trials. N Engl J Med 307: 1180–1182, 1982

    Google Scholar 

  2. Strone GW, Brodie BR, Griffin JJ, Morice MC, Constantini C: Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: In hospital and 30-day results of the PAMI stent pilot trial. J Am Col Cardiol 31: 23–30, 1998

    Google Scholar 

  3. Zahn R, Koch A, Rustige J, Schiele R, Wirtzfeld A: Primary angioplasty versus thrombolysis in the treatment of acute myocardial infarction. Am J Cardiol 79: 264–269, 1997

    Google Scholar 

  4. Braun E: Myocardial reperfusion: A double-edged sword. J Clin Invest 76: 1713–1719, 1985

    Google Scholar 

  5. Lucchesi BR: Modulation of leukocyte-mediated myocardial reperfusion injury. Annu Rev Phisiol 52: 561–576, 1990

    Google Scholar 

  6. Gurevitch J, Frolkis I, Yuhas Y, Lifschitz-Mercer B, Berger E, Paz Y, Matsa M, Kramer A, Mohr R: Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. J Am Coll Cardiol 30: 1554–1561, 1997

    Google Scholar 

  7. Li D, Zhao L, Liu M, Du X, Ding W, Zhang J, Mehta J: Kinetic of tumor necrosis factor-a in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor-a in acute myocardial infarction. Am Heart J 137: 1145–1152, 1999

    Google Scholar 

  8. Donnahoo KK, Meldrum DR, Shenkar R, Chung CS, Abraham E, Harken AH: Early renal ischemia, with or without reperfusion, activates NFkappaB and increases TNF-alpha bioactivity in the kidney. J Urol 163: 1328–1332, 2000

    Google Scholar 

  9. Meldrum KK, Meldrum DR, Meng X, Ao L, Harken AH: TNF-alpha-dependent bilateral renal injury is induced by unilateral renal ischemia-reperfusion. Am J Physiol 282: H540–546, 2002

    Google Scholar 

  10. Rodriguez-Reynoso S, Leal C, Portilla E, Olivares N, Muniz J: Effect of exogenous melatonin on hepatic energetic status during ischemia/reperfusion: Possible role of tumor necrosis factor-alpha and nitric oxide. J Surg Res 100: 141–149, 2001

    Google Scholar 

  11. Yamamoto S, Tanabe M, Wakabayashi G, Shimazu M, Matsumoto K, Kitajima M: The role of tumor necrosis factor-alpha and interleukin-1beta in ischemia-reperfusion injury of the rat small intestine. J Surg Res 99: 134–141, 2001

    Google Scholar 

  12. Song W, Lu X, Feng Q: Tumor necrosis factor-alpha induces apoptosis via inducible nitric oxide synthase in neonatal mouse cardiomyocytes. Cardiovasc Res 45: 595–602, 2000

    Google Scholar 

  13. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, Thompson M, Giroir B: Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. Circulation 97: 1375–1381, 1998

    Google Scholar 

  14. Gottlieb RA, Burleson KO, Kloner RA, Bablor BM, Engler RL: Reperfusion injury induced apoptosis in rabbit cardiomyocytes. J Clin Invest 94: 1621–1628, 1994

    Google Scholar 

  15. Yaoita H, Ogawa K, Maehara K, Maruyama Y: Attenuation of ischemia/reperfusion injury in rats by a caspase inhibitor. Circulation 97: 276–281, 1998

    Google Scholar 

  16. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P: Apoptotic and necrotic myocyte cell death are independent contributing valiables of infarct size in rats. Lab Invest 74: 86–107, 1996

    Google Scholar 

  17. Seckinger P, Isaaz S, Dayer JM: Purification and biologic characterization of a specific tumor necrosis factor-a inhibitor. J Biol Chem 264: 11966–11973, 1989

    Google Scholar 

  18. Engelmann H, Aderka D, Rubinstein M, Rotman D, Wallach D: Tumor necrosis factor-binding protein purified to homogeneity from human urine protects cell from tumor necrosis factor toxicity. J Biol Chem 264: 11974–11980, 1989

    Google Scholar 

  19. Selinsky CL, Boroughs KL, Halsey Jr WA, Howell MD: Multifaceted inhibition of anti-tumor immune mechanisms by soluble tumor necrosis factor receptor type I. Immunology 94: 88–93, 1998

    Google Scholar 

  20. Su X, Zhou T, Yang P, Edwards III C, Mountz JD: Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor. Arthritis Rheum 41: 139–149, 1998

    Google Scholar 

  21. Sugano M, Koyanagi M, Tsuchida K, Hata T, Makino N: In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial infarction. FASEB J 16: 1421–1422, 2002

    Google Scholar 

  22. Himmler A, Maurer-Fogy I, Kronke M, Scheurich P, Pfizenmaier K, Lantz M, Olsson I, Hauptmann R, Stratowa C, Adolf GR: Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein. DNA Cell Biol 9: 705–715, 1990

    Google Scholar 

  23. Makino N, Hata T, Sugano M, Dixon IMC, Yanaga T: Regression of hypertrophy after myocardial infarction is produced by the chronic blockade of angiotensin type 1 receptor in rats. J Mol Cell Cardiol 28: 507–517, 1996

    Google Scholar 

  24. Sugano M, Tsuchida K, Makino N: High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis. Biochem Biophys Res Commun 272: 872–876, 2000

    Google Scholar 

  25. Takeshita S, Isshiki T, Sato T: Increased expression of direct gene transfer into skeletal muscles observed after acute ischemic injury in rats. Lab Invest 74: 1061–1065, 1996

    Google Scholar 

  26. Tsurumi Y, Kearney M, Chen D, Siver M, Takeshita S, Yang J, Symes JF, Isner JM: Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation 96(suppl II): II-382–II-388, 1997

    Google Scholar 

  27. Stamm C, Friehs I, Cowan DB, Moran AM, Cao-Danh H, Duebener LF, del Nido PJ, McGowan FX Jr: Inhibition of tumor necrosis factor-alpha improves postischemic recovery of hypertrophied hearts. Circulation 104(suppl I): I-350–I-355, 2001

    Google Scholar 

  28. Yoshida H, Zhang JJ, Chao L, Chao J: Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion. Hypertension 35: 25–31, 2000

    Google Scholar 

  29. Entman ML, Smith CW: Postreperfusion inflammation: A model for reaction to injury in cardiovascular disease. Cardiovasc Res 28: 1301–1311, 1994

    Google Scholar 

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Authors and Affiliations

  1. Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Tsurumihara, Beppu, Oita, Japan.

    Masahiro Sugano, Tomoji Hata, Keiko Tsuchida, Nobuhiro Suematsu, Jun-ichi Oyama, Shinji Satoh & Naoki Makino

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  1. Masahiro Sugano
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  2. Tomoji Hata
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  3. Keiko Tsuchida
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  4. Nobuhiro Suematsu
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  5. Jun-ichi Oyama
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  6. Shinji Satoh
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  7. Naoki Makino
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Sugano, M., Hata, T., Tsuchida, K. et al. Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats. Mol Cell Biochem 266, 127–132 (2004). https://doi.org/10.1023/B:MCBI.0000049149.03964.c9

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