A Panoramic View of Ferroptosis in Cardiovascular Disease

Abstract

Background: Cardiovascular disease (CVD) remains the leading cause of disease burden worldwide. Ferroptosis, an iron-dependent form of programmed cell death, is characterized by the lethal accumulation of lipid peroxidation, which is morphologically, biochemically and genetically distinct from apoptosis, necrosis and pyroptosis. Emerging evidence provides exciting novel insights to allow for a deeper understanding of the physiology and pathology of ferroptosis in CVD. Summary: The rapidly evolving insights into ferroptosis have revealed its role in the pathogenesis of diverse forms of CVD, including cardiomyopathy, heart failure, atherosclerosis, pulmonary arterial hypertension and cerebrovascular disease. Various types of metabolic pathways are involved in the regulation of ferroptosis, including iron metabolism, lipid metabolism and oxidative metabolism. Modulators of ferroptosis, such as several clinical drugs, preclinical compounds and other emerging materials, have been applied as promising approaches in the prevention and treatment of CVD. Key message: In this review, we provide a 360-degree view of the latest progress in the field of ferroptosis in CVD, highlight the pathogenic role of ferroptosis in CVD and also discuss the importance and future directions of targeting ferroptosis in CVD.

A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives

“…Excess iron is stored in the cytoplasm as ferritin light chain (FTL) and ferritin heavy chain 1 (FTH1). In addition, various proteins such as ferroportin 1 (FPN1) have played an important role in iron metabolism, and for more information, refer to the work of Min and colleagues [2].…”

“…The cystine/glutamate reverse transporter (System Xc−) comprises the light-chain subunit (SLC7A11) and the heavy-chain subunit (SLC3A2), forming a heterodimer via disulfide bonds. This system is essential for cellular antioxidant defense, and more details can be found in the publication by Min and colleagues [2].…”

“…GPX4, a selenium protein in mammals, repairs lipid oxidative damage by converting reduced GSH to oxidized glutathione (GSSG) and toxic lipid hydrogen peroxide (L-OOH) to nontoxic lipid alcohol (L-OH), safeguarding cell membrane integrity from oxidative interference and damage. For more detailed descriptions, refer to the work of Min and colleagues [2].…”

“…Therefore, Nrf2 can inhibit ferroptosis. For more detailed descriptions, refer to the work of Min and colleagues [2].…”

“…1) [9]. For more detailed descriptions, refer to the work of Min and colleagues [2]. AMPK AMPK, a vital intracellular energy metabolism sensor, orchestrates multiple metabolic pathways and balances energy supply and demand [10].…”