Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases

• Published in: Biomedicine & pharmacotherapy Vol. 176; p. 116761
• Main Authors: Zhang, Zeyu, Yang, Zhihua, Wang, Shuai, Wang, Xianliang, Mao, Jingyuan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2024; Elsevier
• Subjects: abnormal iron metabolism; cardiovascular diseases; ferroptosis; glutamate/cystine transport blockage; lipid peroxidation; ZIP; Res; TNFα; MLK3; CPR; CLP; DMT1; HO; NRCM; MDA; SLC7A11; STEAP; DFO; BACH1; ELAVL1; I/R; DFP; Glu; 4-HNE; OGD/R; FTH1; DFX; STZ; CYP; abnormal iron metabolism; HH/R; IL; GPX4; NFκB; SCARA5; Cytc; PUFA; NCOA4; ACSL4; MSOX; AM; lipid peroxidation; CVD; LOX; TFR1; CAT; ROS; DXM; AMPK; Lip1; TLR4; Fer1; FTL; FTN; ferroptosis; BMSC; FPN; NT; CoQ10; DXZ; H/R; HO-1; SLC3A2; ICA69; LPS; INS; CSE; NRF2; RIPK; COX2; ZPP; CD62P; GSH; GSSG; HSP90; System xc; MLKL; NMC; LID; PLOOH; cardiovascular diseases; ACO; LAD; P53; glutamate/cystine transport blockage; PLOH; TF; ATG; PE; LPCAT3; SOR; XO; 3-MA; NOX4; PLOO; PL; PUMA; MCT
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116761

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field. [Display omitted] •Ferroptosis is crucial in numerous cardiovascular diseases (CVDs).•Ferroptosis interacts with other cell death modes in CVDs.•Modulating iron, lipid metabolism, and antioxidants can inhibit ferroptosis in CVDs.•Ferroptosis inhibitor development brings new hope for CVD treatment.•Ferroptosis mechanisms in various CVDs must be further revealed.