© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Expression of apoptosis-related proteins in experimental coxsackievirus myocarditis
Division of Cardiology, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System, Audie L. Murphy Division, 7703 Floyd Curl Drive, San Antonio, TX 78284-7872, USA
* Corresponding author. Tel.: +1 (210) 567 4600; Fax +1 (210) 567 6960; E-mail: freeman@uthscsa.edu
Objective: The extent to which apoptosis contributes to myocyte cell loss during acute carditic viral infection is unknown. To assess whether apoptosis occurs in acute viral myocarditis, and how it is modulated, we studied mice inoculated with coxsackievirus B3 (CVB3). Methods: Five CD1 and C3H.HeJ (C3H) mice/group were sacrificed as saline vehicle-injected controls, and at 1, 2, and 3 weeks post-inoculation (p.i.) with 5x106 pfu CVB3. Histopathological status and terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assays quantified inflammation, necrosis and apoptosis in myocardium. Apoptosis-related protein immunoreactivity defined presence and location of Bax, Fas, Fas Ligand (FasL), Bcl-2, interleukin-1β converting enzyme (ICE), inducible nitric oxide synthase (iNOS) and the proto-oncogene p53. Results: Both strains exhibited significant histopathology at all time points. Saline-injected control animals showed no signs of inflammation and no significant difference in apoptosis-related protein immunoreactivity was observed between strains. Myocardial TUNEL-positive cells were exceedingly rare though apoptosis was present in thymic medulla and spleen follicles. Pro-apoptotic proteins Bax, Fas, and FasL were present in all groups though no clear correlation with histopathology was apparent. By contrast, the anti-apoptotic protein Bcl-2 showed mild immunoreactivity in controls, which increased following infection and correlated well with histopathological scores in both strains. Myocardial iNOS immunoreactivity displayed a similar though weaker staining pattern to Bcl-2 over the 3 week study period in both strains. Neither ICE nor p53 immunoreactivity could be demonstrated in myocardium. Conclusion: Thus, despite marked inflammatory activity, myocyte apoptosis is rare in acute CVB3 myocarditis in CD1 and C3H.HeJ mice.
KEYWORDS CD1; C3H.HeJ; Mice; Coxsackievirus; Myocarditis; Apoptosis; Immunohistochemistry
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Venteo, T. Bourlet, F. Renois, F. Douche-Aourik, J.-F. Mosnier, G. Lorain De la Grand Maison, M. Pluot, B. Pozzetto, and L. Andreoletti Enterovirus-related activation of the cardiomyocyte mitochondrial apoptotic pathway in patients with acute myocarditis Eur. Heart J., November 19, 2009; (2009) ehp489v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. DeBiasi, B. A. Robinson, B. Sherry, R. Bouchard, R. D. Brown, M. Rizeq, C. Long, and K. L. Tyler Caspase Inhibition Protects against Reovirus-Induced Myocardial Injury In Vitro and In Vivo J. Virol., October 15, 2004; 78(20): 11040 - 11050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakamura, A. Sakudo, K. Saeki, T. Kaneko, Y. Matsumoto, A. Toniolo, S. Itohara, and T. Onodera Transfection of prion protein gene suppresses coxsackievirus B3 replication in prion protein gene-deficient cells J. Gen. Virol., December 1, 2003; 84(12): 3495 - 3502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Zhang, B. Yanagawa, P. Cheung, H. Luo, J. Yuan, D. Chau, A. Wang, L. Bohunek, J. E. Wilson, B. M. McManus, et al. Nip21 Gene Expression Reduces Coxsackievirus B3 Replication by Promoting Apoptotic Cell Death via a Mitochondria-Dependent Pathway Circ. Res., June 28, 2002; 90(12): 1251 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Colston, B. Chandrasekar, and G. L. Freeman A Novel Peroxide-induced Calcium Transient Regulates Interleukin-6 Expression in Cardiac-derived Fibroblasts J. Biol. Chem., June 21, 2002; 277(26): 23477 - 23483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Huber, C. Shi, and R. C. Budd {gamma}{delta} T Cells Promote a Th1 Response during Coxsackievirus B3 Infection In Vivo: Role of Fas and Fas Ligand J. Virol., June 5, 2002; 76(13): 6487 - 6494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Seko, N. Kayagaki, K.-i. Seino, H. Yagita, K. Okumura, and R. Nagai Role of Fas/FasL pathway in the activation of infiltrating cells in murine acute myocarditis caused by Coxsackievirus B3 J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1399 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Luo, B. Yanagawa, J. Zhang, Z. Luo, M. Zhang, M. Esfandiarei, C. Carthy, J. E. Wilson, D. Yang, and B. M. McManus Coxsackievirus B3 Replication Is Reduced by Inhibition of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway J. Virol., March 7, 2002; 76(7): 3365 - 3373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Peng, T. Sadusky, Y. Li, G. R. Coulton, H. Zhang, and L. C. Archard Altered expression of Bag-1 in Coxsackievirus B3 infected mouse heart Cardiovasc Res, April 1, 2001; 50(1): 46 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. DeBiasi, C. L. Edelstein, B. Sherry, and K. L. Tyler Calpain Inhibition Protects against Virus-Induced Apoptotic Myocardial Injury J. Virol., January 1, 2001; 75(1): 351 - 361. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Fuse, M. Kodama, Y. Okura, M. Ito, S. Hirono, K. Kato, H. Hanawa, and Y. Aizawa Predictors of Disease Course in Patients With Acute Myocarditis Circulation, December 5, 2000; 102(23): 2829 - 2835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Fox, B. J. Maron, C. Basso, S.-K. Liu, and G. Thiene Spontaneously Occurring Arrhythmogenic Right Ventricular Cardiomyopathy in the Domestic Cat : A New Animal Model Similar to the Human Disease Circulation, October 10, 2000; 102(15): 1863 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dorner, M. Pauschinger, P. L. Schwimmbeck, U. Kuhl, and H.-P. Schultheiss The shift in the myocardial adenine nucleotide translocator isoform expression pattern is associated with an enteroviral infection in the absence of an active T-cell dependent immune response in human inflammatory heart disease J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1778 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Henke, H. Launhardt, K. Klement, A. Stelzner, R. Zell, and T. Munder Apoptosis in Coxsackievirus B3-Caused Diseases: Interaction between the Capsid Protein VP2 and the Proapoptotic Protein Siva J. Virol., May 1, 2000; 74(9): 4284 - 4290. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Calabrese, A. Angelini, G. Thiene, C. Basso, A. Nava, and M. Valente No detection of enteroviral genome in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy J. Clin. Pathol., May 1, 2000; 53(5): 382 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. L van Heerde, S. Robert-Offerman, E. Dumont, L. Hofstra, P. A Doevendans, J. F.M Smits, M. J.A.P Daemen, and C. P.M Reutelingsperger Markers of apoptosis in cardiovascular tissues: focus on Annexin V Cardiovasc Res, February 1, 2000; 45(3): 549 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Huber T cells expressing the {gamma}{delta} T cell receptor induce apoptosis in cardiac myocytes Cardiovasc Res, February 1, 2000; 45(3): 579 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rezvani, J.D. Barrans, K.-S. Dai, and C.-C. Liew Apoptosis-related genes expressed in cardiovascular development and disease: an EST approach Cardiovasc Res, February 1, 2000; 45(3): 621 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zaragoza, C. J. Ocampo, M. Saura, C. Bao, M. Leppo, A. Lafond-Walker, D. R. Thiemann, R. Hruban, and C. J. Lowenstein Inducible Nitric Oxide Synthase Protection Against Coxsackievirus Pancreatitis J. Immunol., November 15, 1999; 163(10): 5497 - 5504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar, D. H. Mitchell, J. T. Colston, and G. L. Freeman Regulation of CCAAT/Enhancer Binding Protein, Interleukin-6, Interleukin-6 Receptor, and gp130 Expression During Myocardial Ischemia/Reperfusion Circulation, January 26, 1999; 99(3): 427 - 433. [Abstract] [Full Text] [PDF]
|
|