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Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases
Zeyu Zhang1, Zhihua Yang1, Shuai Wang2
1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China; Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Abstract:
The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.
Insights
Ferroptosis, an iron-dependent cell death, drives cardiovascular diseases (CVDs). Understanding ferroptosis mechanisms and its role in various CVDs offers new therapeutic strategies for heart conditions.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Cell Death Mechanisms
Background:
- Regulatory cell death processes are key to cardiovascular disease (CVD) therapeutics.
- Ferroptosis, a form of regulated cell death involving lipid peroxidation, significantly contributes to CVD development.
- Understanding ferroptosis is crucial for advancing CVD treatment strategies.
Purpose of the Study:
- To review the concept, mechanisms, and regulation of ferroptosis.
- To explore the role and therapeutic potential of ferroptosis in various CVDs.
- To provide a comprehensive overview of ferroptosis in CVDs for therapeutic innovation.
Main Methods:
- Literature review of ferroptosis and its role in cardiovascular diseases.
- Analysis of ferroptosis mechanisms including iron metabolism and lipid peroxidation.
- Examination of ferroptosis in both common and less-studied CVDs.
Main Results:
- Ferroptosis differs from apoptosis, autophagy, and necrosis.
- Key regulators include the cystine/glutamate transporter, iron metabolism, and lipid peroxidation.
- Ferroptosis is implicated in coronary atherosclerotic heart disease, myocardial infarction, heart failure, and more.
Conclusions:
- Ferroptosis plays a significant role across a spectrum of cardiovascular diseases.
- Targeting ferroptosis presents promising therapeutic avenues for CVDs.
- Further research into ferroptosis could drive innovation in cardiovascular medicine.
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