Ferroptosis as a target for protection against cardiomyopathy

• DOI: 10.1073/pnas.1821022116
• Publication Date: 2019-01-29T01:28:23Z
• Authors: Xuexian Fang; Hao Wang; Dan Han; Enjun Xie; Xiang Yang; Jiayu Wei; Shanshan Gu; Feng Gao; Nali Zhu; Xiangju Yin; Qi Cheng; Pan Zhang; Wei Dai; Jinghai Chen; Fuquan Yang; Huang-Tian Yang; Andreas Linkermann; Wei Gu; Junxia Min; Fudi Wang
• Keywords: Mice, Knockout; 0303 health sciences; NF-E2-Related Factor 2; Iron; Apoptosis; Heme; Mitochondria, Heart; Up-Regulation; 3. Good health; Mice; 03 medical and health sciences; PNAS Plus; Doxorubicin; Reperfusion Injury; Animals; Myocytes, Cardiac; Lipid Peroxidation; Cardiomyopathies; Heme Oxygenase-1

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, newly defined iron-dependent death, mediates both chemotherapy- ischemia/reperfusion-induced cardiomyopathy. RNA-sequencing analysis revealed up-regulation heme oxygenase 1 by doxorubicin as major mechanism ferroptotic As result, degrades releases free iron cardiomyocytes, which turn leads to generation oxidized lipids the mitochondria membrane. Most importantly, chelation therapy pharmacologically blocking ferroptosis could significantly alleviate cardiomyopathy mice. These findings suggest targeting strategy for treating deadly heart disease.