© 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
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