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Regulated cell death pathways in cardiomyopathy

Acta Pharmacologica Sinica volume 44, pages 1521–1535 (2023)Cite this article

Abstract

Heart disease is a worldwide health menace. Both intractable primary and secondary cardiomyopathies contribute to malignant cardiac dysfunction and mortality. One of the key cellular processes associated with cardiomyopathy is cardiomyocyte death. Cardiomyocytes are terminally differentiated cells with very limited regenerative capacity. Various insults can lead to irreversible damage of cardiomyocytes, contributing to progression of cardiac dysfunction. Accumulating evidence indicates that majority of cardiomyocyte death is executed by regulating molecular pathways, including apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Importantly, these forms of regulated cell death (RCD) are cardinal features in the pathogenesis of various cardiomyopathies, including dilated cardiomyopathy, diabetic cardiomyopathy, sepsis-induced cardiomyopathy, and drug-induced cardiomyopathy. The relevance between abnormity of RCD with adverse outcome of cardiomyopathy has been unequivocally evident. Therefore, there is an urgent need to uncover the molecular and cellular mechanisms for RCD in order to better understand the pathogenesis of cardiomyopathies. In this review, we summarize the latest progress from studies on RCD pathways in cardiomyocytes in context of the pathogenesis of cardiomyopathies, with particular emphasis on apoptosis, necroptosis, ferroptosis, autophagy, and pyroptosis. We also elaborate the crosstalk among various forms of RCD in pathologically stressed myocardium and the prospects of therapeutic applications targeted to various cell death pathways.

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Fig. 1: Schematic illustration of apoptosis pathway and apoptosis in cardiomyopathies.
Fig. 2: Schematic illustration of necroptosis pathway and necroptosis in cardiomyopathies.
Fig. 3: Schematic illustration of ferroptosis pathway and ferroptosis in cardiomyopathies.
Fig. 4: Schematic illustration of autophagy pathway and autophagy in cardiomyopathies.
Fig. 5: Schematic illustration of pyroptosis pathway and pyroptosis in cardiomyopathies.
Fig. 6: Schematic illustration of therapeutic potential targeted to intervene regulated cell death.

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Authors and Affiliations

  1. Department of Cardiology, Zhejiang University School of Medicine, Second Affiliated Hospital, Hangzhou, 310009, China

    Shu-yuan Sheng, Jia-min Li, Xin-yang Hu & Yibin Wang

  2. Signature Program in Cardiovascular and Metabolic Diseases, DukeNUS Medical School and National Heart Center of Singapore, Singapore, Singapore

    Yibin Wang

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  1. Shu-yuan Sheng
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  2. Jia-min Li
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  3. Xin-yang Hu
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  4. Yibin Wang
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Correspondence to Yibin Wang.

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Sheng, Sy., Li, Jm., Hu, Xy. et al. Regulated cell death pathways in cardiomyopathy. Acta Pharmacol Sin 44, 1521–1535 (2023). https://doi.org/10.1038/s41401-023-01068-9

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