doi: 10.1161/01.RES.0000143717.70275.8f
© 2004 American Heart Association, Inc.
Editorials |
"Fas-ten" Your Seat Belt
Anti-apoptotic Treatment in Heart Failure Takes Off
From the Department of Cardiology, Campus Virchow Clinic, Charitè, Humboldt University, Berlin, Germany.
Correspondence to Rüdiger von Harsdorf, MD, Medizinische Klinik mit Schwerpunkt Kardiologie, Universitätsklinikum Charitè, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail ruediger.harsdorf@charite.de
See related article, pages 627–636
Key Words: apoptosis • cell signaling/signal transduction • gene regulation
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Despite all efforts in its pharmaceutical treatment, heart failure is still a major cause of morbidity and mortality worldwide.1 Within the past decade, we have witnessed accumulating evidence that cardiomyocyte apoptosis is part of the phenotype of the failing myocardium.2 Most likely because of differences in the absolute number of cells affected, which have ranged by several orders of magnitude in various studies, the causal role of apoptosis in the pathogenesis of heart failure has been brought into question.
Programmed cell death (apoptosis) is an energy-requiring, active form of cell death. As such, it is a fundamental integral part of normal organ development in the first place. Additionally, in all organ systems, apoptosis represents the major mechanism to prevent uncontrolled tumor growth.3
Apoptosis is executed by a family of ubiquitously expressed cysteine proteases termed caspases. Caspases are present in the cell as inactive procaspases that are cleaved and activated in response to apoptotic stimuli. Initial activation of caspases is brought about by at least 2 overlapping signaling pathways. One is characterized by the release of mitochondrial cytochrome c and subsequent activation of caspase-9, whereas the other involves the activation of caspase-8 caused by the transduction of a signal from membrane receptors belonging to the tumor necrosis factor receptor (TNF) family, such as Fas and its ligand FasL.3 Both the mitochondrial4,5 and the "death receptor" pathways6,7 have been shown to exist in the heart.
Why Is Apoptosis So Detrimental to the Heart?
Most of our knowledge of apoptotic cell death has come from the study of dividing or undifferentiated
Related Article:
Circ. Res. 2004 95: 627-636.
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