Disulfide Stress and Its Role in Cardiovascular Diseases

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2024 Aug 10

PMID 39127015

Authors

Shaoju Qian

Guanyu Chen

Ruixue Li

Yinghua Ma

Lin Pan

Xiaoping Wang

Xianwei Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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