Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuechu Zhao, Xiaoting Liang, Ting Li, Zhuang Shao, Zhi Cao, Yi Zeng, Xiaofei Yan, Qi Chen, Hao Zhou, Weifeng Li, Guifen Cheng, Yaping Jiang, Xin Li, Yuelin Zhang, Bei Hu
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引用次数: 0

Abstract

Apelin is an endogenous ligand for the Apelin receptor and is a critical protective effector in myocardial infarction (MI). Nevertheless, these protective mechanisms are not fully understood. Ferroptosis is the major driving factor of MI. This study aimed to investigate the effects and underlying regulatory mechanisms of Apelin on cardiomyocyte ferroptosis in MI. A model of MI was induced in adult C57BL/6J wild type (WT) and Apelin knockout (Apelin-/-) mice. Cardiac function was examined by echocardiography 4 weeks post-MI. RNA-seq, histochemical analyses, and Western blotting were applied to examine the effects of Apelin knockout on the transcriptome and pathological remodeling following infarction and the molecular mechanisms. Mice neonatal cardiomyocytes (NCMs) were used to establish the serum deprivation/hypoxia (SD/H) model in vitro. Compared with WT mice, Apelin-/- mice exhibited more severe impairment of cardiac function and increased fibrosis following infarction. Transcriptome and biochemical analyses revealed the involvement of ferroptosis in mediating Apelin function in MI. Ferroptosis-related proteins were significantly increased post-MI in Apelin-/- mice whereas p-AMPK was greatly decreased. Apelin treatment activated the AMPK pathway and thereby inhibited ferroptosis of NCMs induced by SD/H in vitro. These protective effects were partially reversed by AMPK inhibitor. Apelin deficiency aggravated cardiac dysfunction following infarction by activating cardiomyocyte ferroptosis via inhibition of the AMPK pathway. This offers a novel potential therapeutic target for MI treatment.

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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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