Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review

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Abstract

Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

About the authors

Valery I. Podzolkov

Sechenov First Moscow State Medical University (Sechenov University)

Email: tarzimanova@mail.ru
ORCID iD: 0000-0002-0758-5609

д-р мед. наук, проф., зав. каф. факультетской терапии №2, дир. клиники факультетской терапи №2

Russian Federation, Moscow

Aida I. Tarzimanova

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: tarzimanova@mail.ru
ORCID iD: 0000-0001-9536-8307

д-р мед. наук, проф. каф. факультетской терапии №2

Russian Federation, Moscow

Liubov A. Ponomareva

Sechenov First Moscow State Medical University (Sechenov University)

Email: tarzimanova@mail.ru
ORCID iD: 0000-0002-3179-470X

ординатор, каф. факультетской терапии №2

Russian Federation, Moscow

Elena N. Popova

Sechenov First Moscow State Medical University (Sechenov University)

Email: tarzimanova@mail.ru
ORCID iD: 0000-0001-5164-4621

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

Russian Federation, Moscow

Andrey B. Ponomarev

Sechenov First Moscow State Medical University (Sechenov University)

Email: tarzimanova@mail.ru
ORCID iD: 0000-0002-4242-5723

канд. мед. наук, доц. каф. патологической анатомии им. А.И. Струкова

Russian Federation, Moscow

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2. Fig. 1. Regulation of ferroptosis. Inhibition of system xc-deprives cellular cysteine, leading to GSH deletion and GPX4 inactivation. RSL3 inhibits the activity of GPX4 by covalent binding with GPX4. GPX4 inactivation leads to the accumulation of lipid peroxides and final ferroptosis.

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