Ann Thorac Surg 2005;79:1337
© 2005 The Society of Thoracic Surgeons
Original articles: Cardiovascular
INVITED COMMENTARY
Ian M.C. Dixon, PhD,
Josh E. Raizman, BSc
Department of Physiology, University of Manitoba, Room 3038, SBGH Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, Canada
idixon@sbrc.cajraizman@sbrc.ca
The dogma with respect to apoptosis and the biological fate of cardiac myocytes implicates the eventual death of those cells. Graded, suspended, or reversible apoptosis is a relatively unexplored entity in the setting of heart failure or cardiomyopathy. If cells that are expressing apoptotic genes (eg, caspase-3) could be "rescued" or recruited back into the functional myocardium using selective gene therapy emphasizing expression of genes that promote survival, myocytic drop-out in damaged hearts may conceivably be ablated or attenuated. Narula and coworkers have previously described myofibrolytic cells (MFLs) as those with little sarcomeric structure but with intact nuclei [1, 2]. Presumably these cells are former cardiac myocytes that have undergone the loss of sarcomeric proteins. As they claim that these cells may reside for extended periods within the damaged heart, it could be argued that reversibility of the programmed cell death presents an intriguing putative mechanism for myocardial salvage. Certainly the distinction between total cell apoptosis versus cells with little else other than viable nuclei per se is an interesting finding worth pursuing.
In the current issue, Narula and coworkers have proposed that MFLs are characterized by upregulation of both caspase-3 and Bcl2 [3]. Whereas the coexpression of pro-apoptotic and anti-apoptotic genes in the evolution of tissue development (eg, neural crest tissue) is not unusual; the existence of this mechanism in post-myocardial infarction heart is likely to generate controversy. Evidence that MLFs are metabolically active with intact nuclei (upregulation of proliferating cell nuclear antigen) provide the springboard for future work to fully characterize the MFL type. This may include sequential tracking studies to monitor the loss of myofibrillar proteins, and more intriguing, experiments to force their "restoration" to a myocytic phenotype. Finally, if MFLs appear frequently within the border zone of the infarct, then is the infarct and border zone region characterized by cells that exhibit graded anti-apoptotic and pro-apopotic gene expression? These questions may provide fertile ground for further research.
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- Narula N, Arbustina E, Haider N, et al. Although apoptotic, myofibrillarlytic myocytes demonstrate survival instincts. United States and Canadian Academy of Pathology, Chicago; February 2002. Mod Pathol 2002:38A..
- Communal C, Sumandea M, de Tombe P, et al. Functional consequences of caspase activation in cardiac myocytes Proc Natl Acad Sci USA 2002;99:6252-6256.[Abstract/Free Full Text]
- Narula N, Narula J, Zhang PJ, et al. Is the myofibrillarlytic myocyte a forme fruste apoptotic myocyte Ann Thorac Surg 2005;79:1333-1337.[Abstract/Free Full Text]
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