Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy

Abstract

Cardiomyopathies are a clinically heterogeneous group of cardiac diseases characterized by heart muscle damage, resulting in myocardium disorders, diminished cardiac function, heart failure, and even sudden cardiac death. The molecular mechanisms underlying the damage to cardiomyocytes remain unclear. Emerging studies have demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by iron dyshomeostasis and lipid peroxidation, contributes to the development of ischemic cardiomyopathy, diabetic cardiomyopathy, doxorubicin-induced cardiomyopathy, and septic cardiomyopathy. Numerous compounds have exerted potential therapeutic effects on cardiomyopathies by inhibiting ferroptosis. In this review, we summarize the core mechanism by which ferroptosis leads to the development of these cardiomyopathies. We emphasize the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial effects in treating cardiomyopathies. This review suggests that inhibiting ferroptosis pharmacologically may be a potential therapeutic strategy for cardiomyopathy treatment.

Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy

“…Ferroptosis is a form of programmed cell death that relies on iron-catalyzed lipid peroxidation, distinguishing it from autophagy, apoptosis, and necrosis [ 27 ]. Numerous studies have demonstrated the involvement of ferroptosis in myocardial injury, including DCM [ 11 , 28 ]. Our data further substantiate the association between ferroptosis and DCM.…”

“…Ferroptosis, an iron-dependent form of regulatory cell death, is activated in DCM and has been shown to play an indispensable role in its pathogenesis [ 10 ]. The inhibition of cardiomyocyte ferroptosis could alleviate the progression of DCM [ 11 , 12 ]. Ferroptosis is implicated in myocardial injury in type 2 diabetes mellitus (T2DM), and inhibition of retinol dehydrogenase 10 (RDH10) promotes retinol metabolism disorder, thereby promoting ferroptosis in the heart [ 13 ].…”

Exploring Ferroptosis-Associated Gene Signatures as Diagnostic and Therapeutic Targets for Sepsis-Induced Cardiomyopathy

“…Recent insights into iron-mediated programmed cell death, or ferroptosis, have highlighted its crucial role in various pathophysiological conditions [ 5 ], including cardiomyopathies linked to sepsis [ 6 ]. Ferroptosis is characterized by iron accumulation and lipid peroxidation, leading to cell membrane rupture, thus distinguishing it from traditional cell death mechanisms [ 5 ].…”

“…Ferroptosis is characterized by iron accumulation and lipid peroxidation, leading to cell membrane rupture, thus distinguishing it from traditional cell death mechanisms [ 5 ]. Recent studies have elucidated the complex interplay between iron dysregulation and oxidative stress in precipitating ferroptosis within cardiac tissues, significantly contributing to the intricate pathology of SICM [ 6 ]. Targeted modulation of cellular processes, particularly through agents like microRNA-130b-3p and the PARP inhibitor Olaparib, has shown potential in mitigating ferroptosis and improving clinical outcomes in SICM models [ 7 , 8 ].…”