CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Free Radic Res. 2021 Apr;55(4):405-415. doi: 10.1080/10715762.2021.1876856. Epub 2021 Jan 27.
Cardiovascular disease (CVD), including heart attack, stroke, heart failure, arrhythmia, and other congenital heart diseases remain the leading cause of morbidity and mortality worldwide. The leading cause of deaths in CVD is attributed to myocardial infarction due to the rupture of atherosclerotic plaque. Atherosclerosis refers a condition when restricted or even blockage of blood flow occurs due to the narrowing of blood vessels as a result of the buildup of plaques composed of oxidized lipids. It is well-established that free radical oxidation of polyunsaturated fatty acids (PUFAs) in lipoproteins or cell membranes, termed lipid peroxidation (LPO), plays a significant role in atherosclerosis. LPO products are involved in immune responses and cell deaths in this process, in which previous evidence supports the role of programmed cell death (apoptosis) and necrosis. Ferroptosis is a newly identified form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels, which exhibits distinct features from apoptosis, necrosis and autophagy in morphology, biochemistry and genetics. Emerging evidence appears to demonstrate that ferroptosis is also involved in CVD. In this review, we summarize the recent progress on ferroptosis in CVD and atherosclerosis, highlighting the role of free radical LPO. The evidence underlying the ferroptosis and challenges in the field will also be critically discussed.
心血管疾病（CVD），包括心脏病发作、中风、心力衰竭、心律失常和其他先天性心脏病，仍然是全球发病率和死亡率的主要原因。CVD 导致的死亡的主要原因是由于动脉粥样硬化斑块破裂导致的心肌梗死。动脉粥样硬化是指由于斑块的堆积导致血管狭窄，从而出现血流受限甚至阻塞的一种情况，这些斑块由氧化脂质组成。众所周知，脂蛋白或细胞膜中多不饱和脂肪酸（PUFAs）的自由基氧化，即脂质过氧化（LPO），在动脉粥样硬化中起着重要作用。LPO 产物参与了这一过程中的免疫反应和细胞死亡，其中之前的证据支持程序性细胞死亡（细胞凋亡）和坏死的作用。铁死亡是一种新发现的受调控的细胞死亡形式，其特征是脂质过氧化物在铁依赖性作用下积累到致命水平，在形态、生化和遗传学上与细胞凋亡、坏死和自噬有明显的不同。新出现的证据表明，铁死亡也与 CVD 有关。在这篇综述中，我们总结了铁死亡在 CVD 和动脉粥样硬化中的最新进展，强调了自由基 LPO 的作用。还将批判性地讨论铁死亡的证据基础和该领域的挑战。
