(Circulation. 2001;103:877.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Gene Transfer of Heat-Shock Protein 70 Reduces Infarct Size In Vivo After Ischemia/Reperfusion in the Rabbit Heart
From the Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond (J.C.C., M.L.H., R.C.K.); the Department of Cardiology, Kanazawa Medical University, Ishikawa, Japan (S.O.); the Robert-Roessle-Klinik, Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (O.W.); and Baylor College of Medicine, Houston, Tex (M.R.S.).
Correspondence to Rakesh C. Kukreja, PhD, Professor, Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, 1101 E Marshall St, Richmond, VA 23298. E-mail rakesh{at}hsc.vcu.edu
Background—Heat-shock protein 70 (HSP 70) plays a role in myocardial protection. No studies are available, however, to show that direct gene transfer of HSP 70 reduces myocardial infarction in vivo.
Methods and Results—Rabbit hearts were injected with vehicle or Ad.HSP70 at 3 sites (1.5x109 pfu, 50 µL/site) in the left ventricle (LV). Four days later, hearts were removed, and expression of inducible (HSP 70) and constitutive (HSC 70) proteins was measured in the LV and right ventricle (RV). Subsets of 5 to 7 animals in the vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups were subjected to 30 minutes of ischemia and 3 hours of reperfusion. Infarct size was measured by tetrazolium staining. Increased expression of HSP 70 was observed in LV injected with Ad.HSP70 compared with vehicle-treated hearts. HSP 70 was undetectable in RV, the noninjected region of the heart. The expression of HSC 70 remained unchanged in hearts treated with vehicle or Ad.HSP70. Infarct size (% risk area) decreased to 24.5±2.8 in Ad.HSP70-injected hearts compared with 41.9±2.8 and 42.7±2.5 in the vehicle- and Ad.LacZ-treated hearts (P<0.01). The infarct size was not different between the vehicle- and Ad.LacZ-treated hearts (P>0.05). The risk areas (% of LV) were not different among the 3 groups, ie, 50.1±5.2, 47.7±3.5, and 53.3±2.9 in vehicle-, Ad.lacZ-, and Ad.HSP70-treated groups (P>0.05).
Conclusions—Direct gene delivery of HSP 70 in vivo reduces the severity of ischemic injury in the heart.
Key Words: myocardial infarction • ischemia • proteins • genes • viruses
This article has been cited by other articles:
 |
|
 |
|
  M. Sakabe, A. Shiroshita-Takeshita, A. Maguy, B. J.J.M. Brundel, A. Fujiki, H. Inoue, and S. Nattel Effects of a heat shock protein inducer on the atrial fibrillation substrate caused by acute atrial ischaemia Cardiovasc Res, April 1, 2008; 78(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tang, R. Kang, W. Xiao, H. Wang, S. K. Calderwood, and X. Xiao The Anti-inflammatory Effects of Heat Shock Protein 72 Involve Inhibition of High-Mobility-Group Box 1 Release and Proinflammatory Function in Macrophages J. Immunol., July 15, 2007; 179(2): 1236 - 1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shamaei-Tousi, J. P. Halcox, and B. Henderson Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease Cardiovasc Res, April 1, 2007; 74(1): 19 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Belke, B. Gloss, J. M. Hollander, E. A. Swanson, H. Duplain, and W. H. Dillmann In vivo gene delivery of HSP70i by adenovirus and adeno-associated virus preserves contractile function in mouse heart following ischemia-reperfusion Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2905 - H2910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhu, H. Zhao, A. R. Graveline, E. S. Buys, U. Schmidt, K. D. Bloch, A. Rosenzweig, and W. Chao MyD88 and NOS2 are essential for Toll-like receptor 4-mediated survival effect in cardiomyocytes Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1900 - H1909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bak, I. Lekli, B. Juhasz, N. Nagy, E. Varga, J. Varadi, R. Gesztelyi, G. Szabo, L. Szendrei, I. Bacskay, et al. Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1329 - H1336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-K. Kim, J. Suarez, Y. Hu, P. M. McDonough, C. Boer, D. J. Dix, and W. H. Dillmann Deletion of the Inducible 70-kDa Heat Shock Protein Genes in Mice Impairs Cardiac Contractile Function and Calcium Handling Associated With Hypertrophy Circulation, June 6, 2006; 113(22): 2589 - 2597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nordlie, L. E. Wold, B. Z. Simkhovich, C. Sesti, and R. A. Kloner Molecular Aspects of Ischemic Heart Disease: Ischemia/Reperfusion-Induced Genetic Changes and Potential Applications of Gene and RNA Interference Therapy Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 17 - 30. [Abstract] [PDF]
|
|
|
|
 |
|
 A. S. Pachori, L. G. Melo, L. Zhang, S. D. Solomon, and V. J. Dzau Chronic Recurrent Myocardial Ischemic Injury Is Significantly Attenuated by Pre-Emptive Adeno-Associated Virus Heme Oxygenase-1 Gene Delivery J. Am. Coll. Cardiol., February 7, 2006; 47(3): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Grossin, C. Cournil-Henrionnet, A. Pinzano, N. Gaborit, D. Dumas, S. Etienne, J. F. Stoltz, B. Terlain, P. Netter, L. M. Mir, et al. Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis FASEB J, January 1, 2006; 20(1): 65 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-C. Fan, X. Ren, J. Qian, Q. Yuan, P. Nicolaou, Y. Wang, W. K. Jones, G. Chu, and E. G. Kranias Novel Cardioprotective Role of a Small Heat-Shock Protein, Hsp20, Against Ischemia/Reperfusion Injury Circulation, April 12, 2005; 111(14): 1792 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang Prenatal Hypoxia and Cardiac Programming Reproductive Sciences, January 1, 2005; 12(1): 2 - 13. [Abstract] [PDF]
|
|
|
|
|
|
S. Okubo, Y. Tanabe, K. Takeda, M. Kitayama, S. Kanemitsu, R. C. Kukreja, and N. Takekoshi Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of {delta}-opioid receptor Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1786 - H1791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ren, R. Strube, X. Zhang, S.-Y. Chen, and X. F. Huang Potent Tumor-Specific Immunity Induced by an In vivo Heat Shock Protein-Suicide Gene-Based Tumor Vaccine Cancer Res., September 15, 2004; 64(18): 6645 - 6651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bolli, L. Becker, G. Gross, R. Mentzer Jr, D. Balshaw, and D. A. Lathrop Myocardial Protection at a Crossroads: The Need for Translation Into Clinical Therapy Circ. Res., July 23, 2004; 95(2): 125 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, S. Bae, and L. Zhang Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat heart Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1712 - H1719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. MELO, A. S. PACHORI, D. KONG, M. GNECCHI, K. WANG, R. E. PRATT, and V. J. DZAU Gene and cell-based therapies for heart disease FASEB J, April 1, 2004; 18(6): 648 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. L. Tang, Y. Tang, Y. C. Zhang, K. Qian, L. Shen, and M. I. Phillips Protection From Ischemic Heart Injury by a Vigilant Heme Oxygenase-1 Plasmid System Hypertension, April 1, 2004; 43(4): 746 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C Chi and J. S Karliner Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors Cardiovasc Res, February 15, 2004; 61(3): 437 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. McMullen, T. Shioi, W.-Y. Huang, L. Zhang, O. Tarnavski, E. Bisping, M. Schinke, S. Kong, M. C. Sherwood, J. Brown, et al. The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110{alpha}) Pathway J. Biol. Chem., February 6, 2004; 279(6): 4782 - 4793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Yaglom, D. Ekhterae, V. L. Gabai, and M. Y. Sherman Regulation of Necrosis of H9c2 Myogenic Cells upon Transient Energy Deprivation: RAPID DEENERGIZATION OF MITOCHONDRIA PRECEDES NECROSIS AND IS CONTROLLED BY REACTIVE OXYGEN SPECIES, STRESS KINASE JNK, HSP72, AND ARC J. Biol. Chem., December 12, 2003; 278(50): 50483 - 50496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rafiee, Y. Shi, K. A. Pritchard Jr., H. Ogawa, A. L. W. Eis, R. A. Komorowski, C. M. Fitzpatrick, J. S. Tweddell, S. B. Litwin, K. Mussatto, et al. Cellular Redistribution of Inducible Hsp70 Protein in the Human and Rabbit Heart in Response to the Stress of Chronic Hypoxia: ROLE OF PROTEIN KINASES J. Biol. Chem., October 31, 2003; 278(44): 43636 - 43644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Z. Simkhovich, P. Marjoram, C. Poizat, L. Kedes, and R. A. Kloner Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study Cardiovasc Res, August 1, 2003; 59(2): 450 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Hampton, A. Shimamoto, C. L. Rothnie, J. Griscavage-Ennis, A. Chong, D. J. Dix, E. D. Verrier, and T. H. Pohlman HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H866 - H874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Cappola, L. Cope, A. Cernetich, L. A. Barouch, K. Minhas, R. A. Irizarry, G. Parmigiani, S. Durrani, T. Lavoie, E. P. Hoffman, et al. Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy Physiol Genomics, June 24, 2003; 14(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. LaPointe, X.-P. Yang, O. A. Carretero, and Q. He Left ventricular targeting of reporter gene expression in vivo by human BNP promoter in an adenoviral vector Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1439 - H1445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jayakumar, K. Suzuki, I. A. Sammut, R. T. Smolenski, M. Khan, N. Latif, H. Abunasra, B. Murtuza, M. Amrani, and M. H. Yacoub Heat Shock Protein 70 Gene Transfection Protects Mitochondrial and Ventricular Function Against Ischemia-Reperfusion Injury Circulation, September 18, 2001; 104(90001): I-303 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tekin, L. Xi, T. Zhao, M. I. Tejero-Taldo, S. Atluri, and R. C. Kukreja Mitogen-activated protein kinases mediate heat shock-induced delayed protection in mouse heart Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H523 - H532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. FRANCIS, M. K. RAIZADA, A. A. MANGI, L. G. MELO, V. J. DZAU, P. R. VALE, J. M. ISNER, D. W. LOSORDO, J. CHAO, M. J. KATOVICH, et al. Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb? Physiol Genomics, December 21, 2001; 7(2): 79 - 94. [Abstract] [Full Text] [PDF]
|
|