This review paper below tells the role of ferroptosis in atherosclerosis. There are many papers supporting the role of ferroptosis in atherosclerosis, but there are also other opinions. So the discussion will continue and looks like one day ATH434 will be tested in this sense if ATH434 can slow down atherosclerosis.

The paper by Daniel Kosman et al, 2021 (The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells) comes very close to these mechanisms and gives me (perhaps only me) some support that ATH434 could prevent atherosclerosis and just by preventing ferroptosis of the endothelial cells.

This review is free and here is the abstract:

Review

J Inflamm Res

. 2023 Oct 16:16:4575-4592.

doi: 10.2147/JIR.S430885. eCollection 2023.

The Chains of Ferroptosis Interact in the Whole Progression of Atherosclerosis

Xueqi Wan ^{# 1}, Huan Zhang ^{# 1}, Jinfan Tian ^{# 1}, Peng Hao ¹, Libo Liu ¹, Yuquan Zhou ¹, Jing Zhang ¹, Xiantao Song ¹, Changjiang Ge ¹

Affiliations expand

• PMID: 37868832

PMCID: PMC10588755 DOI: 10.2147/JIR.S430885

Abstract

Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.