Ferroptosis as a target for protection against cardiomyopathy

Abstract

Significance Nonapoptotic cell death-induced tissue damage has been implicated in a variety of diseases, including neurodegenerative disorder, inflammation, and stroke. In this study, we demonstrate that ferroptosis, a newly defined iron-dependent cell death, mediates both chemotherapy- and ischemia/reperfusion-induced cardiomyopathy. RNA-sequencing analysis revealed up-regulation of heme oxygenase 1 by doxorubicin as a major mechanism of ferroptotic cardiomyopathy. As a result, heme oxygenase 1 degrades heme and releases free iron in cardiomyocytes, which in turn leads to generation of oxidized lipids in the mitochondria membrane. Most importantly, both iron chelation therapy and pharmacologically blocking ferroptosis could significantly alleviate cardiomyopathy in mice. These findings suggest targeting ferroptosis as a strategy for treating deadly heart disease.

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Affiliated Institutions

• Shanghai Institutes for Biological Sciences CN
• Columbia University US
• University of Chinese Academy of Sciences CN
• Chinese Academy of Sciences CN
• Institute of Biophysics CN
• University Hospital Carl Gustav Carus DE
• Zhejiang University CN
• Second Affiliated Hospital of Zhejiang University CN
• Technische Universität Dresden DE
• Cancer Genetics (United States) US
• Zhengzhou University CN
• Shanghai Jiao Tong University CN

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