Cardiovascular disease (CVD) is one of the leading causes of mortality in humans, and oxidative stress plays a pivotal role in disease progression. This phenomenon typically arises from weakening of the cellular antioxidant system or excessive accumulation of peroxides. This review focuses on a specialized form of oxidative stress—disulfide stress—which is triggered by an imbalance in the glutaredoxin and thioredoxin antioxidant systems within the cell, leading to the accumulation of disulfide bonds. The genesis of disulfide stress is usually induced by extrinsic pathological factors that disrupt the thiol-dependent antioxidant system, manifesting as sustained glutathionylation of proteins, formation of abnormal intermolecular disulfide bonds between cysteine-rich proteins, or irreversible oxidation of thiol groups to sulfenic and sulfonic acids. Disulfide stress not only precipitates the collapse of the antioxidant system and the accumulation of reactive oxygen species, exacerbating oxidative stress, but may also initiate cellular inflammation, autophagy, and apoptosis through a cascade of signaling pathways. Furthermore, this review explores the detrimental effects of disulfide stress on the progression of various CVDs including atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. This review also proposes several potential therapeutic avenues to improve the future treatment of CVDs.

中文翻译：

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二硫化物应激及其在心血管疾病中的作用


心血管疾病（CVD）是人类死亡的主要原因之一，氧化应激在疾病进展中起着关键作用。这种现象通常是由于细胞抗氧化系统减弱或过氧化物过度积累引起的。这篇综述重点关注一种特殊形式的氧化应激——二硫键应激——它是由细胞内谷氧还蛋白和硫氧还蛋白抗氧化系统不平衡引发的，导致二硫键的积累。二硫键应激的发生通常是由破坏硫醇依赖性抗氧化系统的外在病理因素引起的，表现为蛋白质的持续谷胱甘肽化、富含半胱氨酸的蛋白质之间形成异常的分子间二硫键，或硫醇基团不可逆氧化为硫基和磺酸基酸。二硫键应激不仅会加速抗氧化系统的崩溃和活性氧的积累，加剧氧化应激，而且还可能通过一系列信号通路引发细胞炎症、自噬和细胞凋亡。此外，本综述探讨了二硫键应激对各种心血管疾病进展的不利影响，包括动脉粥样硬化、高血压、心肌缺血再灌注损伤、糖尿病心肌病、心脏肥大和心力衰竭。这篇综述还提出了几种潜在的治疗途径，以改善未来心血管疾病的治疗。