Abstract

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.

摘要

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。心血管疾病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塞。动脉粥样硬化是指由于氧化脂质组成的斑块积聚导致血管变窄而导致血流受限甚至阻塞的情况。众所周知，脂蛋白或细胞膜中多不饱和脂肪酸 (PUFA) 的自由基氧化，称为脂质过氧化 (LPO)，在动脉粥样硬化中起重要作用。LPO产品在这个过程中参与免疫反应和细胞死亡，其中先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调节性细胞死亡形式，其特征在于铁依赖性脂质氢过氧化物积累至致死水平，在形态、生物化学和遗传学方面表现出细胞凋亡、坏死和自噬的不同特征。新出现的证据似乎表明铁死亡也与心血管疾病有关。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。铁死亡背后的证据和该领域的挑战也将进行批判性讨论。其在形态、生物化学和遗传学方面表现出与细胞凋亡、坏死和自噬不同的特征。新出现的证据似乎表明铁死亡也与心血管疾病有关。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。铁死亡背后的证据和该领域的挑战也将进行批判性讨论。其在形态、生物化学和遗传学方面表现出与细胞凋亡、坏死和自噬不同的特征。新出现的证据似乎表明铁死亡也与心血管疾病有关。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。铁死亡背后的证据和该领域的挑战也将进行批判性讨论。