Ferroptosis as a target for protection against cardiomyopathy

Fang, Xuexian; Wang, Hao; Han, Dan; Xie, Enjun; Yang, Xiang; Wei, Jiayu; Gu, Shanshan; Gao, Feng; Zhu, Nali; Yin, Xiangju; Cheng, Qi; Zhang, Pan; Dai, Wei; Chen, Jinghai; Yang, Fuquan; Yang, Huang‐Tian; Linkermann, Andreas; Gu, Wei; Min, Junxia; Wang, Fudi

doi:10.1073/pnas.1821022116

articleProceedings of the National Academy of SciencesJan 28, 2019BRONZE OA

Ferroptosis as a target for protection against cardiomyopathy

XFXuexian Fang HWHao Wang DHDan Han EXEnjun Xie XYXiang Yang

Zhejiang University · Zhengzhou University · +10 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated in mitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice.…

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2,104

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Topics & keywords

Topics

Keywords

Heme oxygenase
Programmed cell death
Cardiomyopathy
Mitochondrion
Heme
Inflammation
Cancer research
Deferoxamine

UN Sustainable Development Goals

Good health and well-being

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