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Role of Cardiomyocyte Apoptosis in Heart Failure

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Biochemistry of Apoptosis and Autophagy

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 18))

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Abstract

Cardiomyocyte apoptosis has now been identified in a wide variety of patients with heart failure as well as in failing hearts due to experimentally induced pathophysiological situations such as myocardial infarction, hemodynamic alterations, and different types of cardiomyopathies. Several mechanisms including oxidative stress, inflammation and intracellular Ca2+-overload have been suggested to induce the release of cytotoxic proteins such as cytochrome C for the activation of caspases -3/-9 and subsequent occurrence of apoptotic cell death. Extensive research has revealed both the up-regulation of pro-apoptotic pathway involving PKC isoforms -α/-ε, NFκB, p38-MAPK and BAX, and down-regulation of anti-apoptotic pathway involving Akt, BAD, Bcl-2 and Erk-1/2 in cardiomyocytes from failing hearts. In view of the critical role of inflammation in heart failure, some evidence has been presented to show the role of TNF-α in the activation and deactivation of cell survival and cell death signal transduction pathways for the occurrence of apoptosis in non-ischemic failing hearts due to volume overload and dilated cardiomyopathy. Although the occurrence of apoptosis in failing hearts can be seen to produce loss of some cardiomyocytes leading to heart dysfunction, no meaningful conclusion can be made regarding the exact role of apoptosis in contractile defects during the development of heart failure.

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Acknowledgements

The infrastructure support for this project was provided by the St. Boniface Hospital Research Foundation, Winnipeg, Canada.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, Max Rady College of Medicine, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, R2H 2A6, Canada

    Sukhwinder K. Bhullar & Naranjan S. Dhalla

  2. Department of Kinesiology, Nutrition and Food Science, California State University, Los Angeles, CA 90032, USA

    Anureet K. Shah

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  1. Sukhwinder K. Bhullar
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  3. Naranjan S. Dhalla
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Correspondence to Naranjan S. Dhalla .

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  1. University of Manitoba, Winnipeg, MB, Canada

    Lorrie A. Kirshenbaum

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Bhullar, S.K., Shah, A.K., Dhalla, N.S. (2022). Role of Cardiomyocyte Apoptosis in Heart Failure. In: Kirshenbaum, L.A. (eds) Biochemistry of Apoptosis and Autophagy. Advances in Biochemistry in Health and Disease, vol 18. Springer, Cham. https://doi.org/10.1007/978-3-030-78799-8_14

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