Myocardial ferroptosis may exacerbate the progression of atrial fibrillation through isolevuglandins

Abstract

Atrial fibrillation (AF) poses a serious health threat to human health and causes various adverse effects. It is currently the most common type of arrhythmia in adults. Long-term AF induces a series of heart-remodeling events, including mainly cardiac structural remodeling and electrical remodeling, which further exacerbates AF. The oxidative stress has been shown to play a role in inducing myocardial remodeling and the progression of AF. Recent studies have shown that ferroptosis occurs in the myocardium of patients with AF, which exacerbates oxidative stress and may constitute a new mechanism for the progression of AF. However, it is unknown to us how ferroptosis is involved in the initiation and maintenance of AF, so the purpose of this review is to elucidate the possible underlying mechanism of ferroptosis exacerbating AF. We reviewed the latest studies on myocardial ferroptosis and AF and speculate that the lipid peroxidation products isolevuglandins (IsoLGs), which are produced during myocardial ferroptosis, may be involved in the progression of AF through two pathways: (1) IsoLGs inhibit the degradation of myocardial collagen, worsening myocardial fibrosis; and (2) IsoLGs promote the occurrence of amyloidosis in the myocardium and increase the risk of AF. Consequently, we aim to prevent the progression of atrial fibrillation by either suppressing the production of IsoLGs or enhancing their clearance process to inhibit ferroptosis in the myocardium, improving the prognosis of patients with AF.

Keywords: Amyloidosis; Atrial fibrillation; Ferroptosis; Isolevuglandins; Myocardial fibrosis; Myocardial remodeling.

Fig. 1

Schematic of ferroptosis pathways in cells (adapted from Hu H et al.[48])

Fig. 2

Molecular pathways of IsoLGs involved in the progression of AF