Review Article“How Do Cardiomyocytes Die?” Apoptosis and Autophagic Cell Death in Cardiac Myocytes
Section snippets
Central Apoptotic Machinery
Apoptosis is mediated by 2 central pathways: the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway.28Fig. 1 illustrates the central parthways of apoptosis. Caspases, a subclass of cysteine proteases that cleave substrates after aspartic acid residues, are thought to be the central executioners of the apoptotic pathway.29 Caspases are highly conserved through evolution and can be found from humans all the way down to insects, nematodes, and hydra.30, 31, 32 In
Apoptosis in the Cardiovascular System
In the last decade, there has been increasing evidence suggesting the importance of apoptosis in the development and progression of cardiovascular disease. Apoptosis has been detected in the myocardium in a number of cardiac pathologies including hypoxia,73 ischemia followed by reperfusion, myocardial infarction, myocardial hypertrophy, and, more recently, in patients with end-stage heart failure.74, 75 Apoptosis has also been detected in atherosclerotic lesions of the vasculature.76
The Role of Autophagic Cell Death in Cardiomyocyte Loss
Autophagic cell death has been demonstrated in neurodegenerative disorders such as Parkinson's and Alzheimer's disease.136, 137 The role of autophagic cell death in heart muscle degeneration has largely remained obscure. Recent studies have demonstrated the existence of autophagic cell death in hypertrophied, failing, and hibernating myocardium.138, 139, 140, 141 Knaapen et al139 examined the cardiac tissue of patients in terminal stage of heart failure secondary to ischemic and dilated
The Possible Relationship Between the Ubiquitin-Proteasome System and Autophagic Cell Death
There are many lines of evidence that connect the autophagic machinery with the ubiquitin-proteasome pathway in cell death.142 The involvement and relationship between autophagic cell death and the ubiquitin-proteasome system in myocardial muscle degeneration/loss has remained relatively obscure. In an effort to examine the different diagnostic criteria of apoptotic cell death in cardiomyocytes, Knaapen et al139 studied the hypothesis of whether TUNEL labeling parallels caspase activation. The
Conclusion
Increasing evidence from both in vivo and in vitro studies suggest a strong role of apoptosis in the development of several cardiovascular diseases. Apoptosis inhibition may thus be a novel and exiting was to treat cardiovascular pathology. However, a significant number of questions regarding the relative contribution of apoptosis to cardiomyocyte death and its clinical relevance remain unclear. Apoptosis is not the only form of death leading to loss of cardiomyocytes, because recent evidence
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