© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Apoptotic versus autophagic cell death in heart failure
aHistoGeneX (Histological Gene Expression Systems), Antwerp, Belgium
bSt. George's Hospital Medical School, London, UK
cDivision of Pharmacology, University of Antwerp, Antwerp, Belgium
dDepartment Pathology, Middelheim Hospital, Lindendreef 1, B-2020 Antwerp, Belgium
* Corresponding author. Postal address: Department of Pathology, Middelheim Hospital, Lindendreef 1, B-2020 Antwerp, Belgium. Tel.: +32-3-280-4815; fax: +32-3-280-4816 mark.kockx{at}uia.ua.ac.be
Objective: Progressive loss of cardiomyocytes is one of the most important pathogenic characteristics of heart failure. Apoptosis may be an important mode of cell death in heart failure but it must be demonstrated by multiple criteria and not just TUNEL staining alone. Previously, we and others have demonstrated that besides apoptosis other phenomena like active gene transcription can result in TUNEL positivity. Moreover, other types of cell death that are caspase-independent could be important in heart failure. This study examined the hypothesis whether TUNEL labeling parallels caspase activation. Methods: Cardiac tissue of patients in the terminal stage of heart failure as a consequence of ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) were studied. Embryonic mice hearts were used for positive control for detection of the classical apoptosis. Results: In mice embryonic hearts we could clearly find apoptotic cell death detected by TUNEL labeling and immunohistochemistry for activated caspase-3. In heart failure, TUNEL-positive cardiomyocytes were negative for active caspase-3 but showed signs of active gene transcription (SC-35). However, autophagic cell death could be found in 0.3% of the cardiomyocytes. Autophagic cell death was demonstrated by granular cytoplasmic ubiquitin inclusions, an established marker of autophagocytosis in neurons. Interestingly, these autophagic cardiomyocytes were TUNEL and activated caspase-3 negative but were also negative for C9, a marker for necrosis. Western blot analysis confirmed that in cardiomyopathies no cleavage of caspase-3 and caspase-7 occurred. Conclusion: The present study demonstrates two fundamentally different situations of cell death in cardiac tissue. In embryonic mice, cardiomyocytes undergo caspase-dependent cell death. However, cardiomyocytes in heart failure show caspase-independent autophagic cell death rather than apoptotic cell death.
KEYWORDS Apoptosis; Heart failure; Cardiomyopathy; Myocytes
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Paris, C. Perez-Pastene, E. Couve, P. Caviedes, S. LeDoux, and J. Segura-Aguilar Copper{middle dot}Dopamine Complex Induces Mitochondrial Autophagy Preceding Caspase-independent Apoptotic Cell Death J. Biol. Chem., May 15, 2009; 284(20): 13306 - 13315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kanamori, G. Takemura, R. Maruyama, K. Goto, A. Tsujimoto, A. Ogino, L. Li, I. Kawamura, T. Takeyama, T. Kawaguchi, et al. Functional Significance and Morphological Characterization of Starvation-Induced Autophagy in the Adult Heart Am. J. Pathol., May 1, 2009; 174(5): 1705 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Martinet and G. R.Y. De Meyer Autophagy in Atherosclerosis: A Cell Survival and Death Phenomenon With Therapeutic Potential Circ. Res., February 13, 2009; 104(3): 304 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Gustafsson and R. A. Gottlieb Autophagy in Ischemic Heart Disease Circ. Res., January 30, 2009; 104(2): 150 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Rothermel and J. A. Hill Autophagy in Load-Induced Heart Disease Circ. Res., December 5, 2008; 103(12): 1363 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maruyama, K. Goto, G. Takemura, K. Ono, K. Nagao, T. Horie, A. Tsujimoto, H. Kanamori, S. Miyata, H. Ushikoshi, et al. Morphological and biochemical characterization of basal and starvation-induced autophagy in isolated adult rat cardiomyocytes Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1599 - H1607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nishida, O. Yamaguchi, and K. Otsu Crosstalk Between Autophagy and Apoptosis in Heart Disease Circ. Res., August 15, 2008; 103(4): 343 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakagawa, G. Takemura, H. Kanamori, K. Goto, R. Maruyama, A. Tsujimoto, T. Ohno, H. Okada, A. Ogino, M. Esaki, et al. Mechanisms by Which Late Coronary Reperfusion Mitigates Postinfarction Cardiac Remodeling Circ. Res., July 3, 2008; 103(1): 98 - 106. [Abstract] [Full Text] [PDF]
|
|