Ferroptosis as a novel therapeutic target for cardiovascular disease

Abstract

Cell death is an important component of the pathophysiology of cardiovascular disease. An understanding of how cardiomyocytes die, and why regeneration of cells in the heart is limited, is a critical area of study. Ferroptosis is a form of regulated cell death that is characterized by iron overload, leading to accumulation of lethal levels of lipid hydroperoxides. The metabolism of iron, lipids, amino acids and glutathione tightly controls the initiation and execution of ferroptosis. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, and heart failure. This article reviews the mechanisms by which ferroptosis is initiated and controlled and discusses ferroptosis as a novel therapeutic target for various cardiovascular diseases.

Role of Ferroptosis in Lung Diseases

“…Previous studies have proven that ferroptosis plays an essential role in the occurrence and progression of various pathological processes and diseases, including intracerebral haemorrhage, 9 ischaemic stroke, 70 sepsis, 71 cancer, 72 and myocardial infarction. 73 More recently, several studies have indicated that ferroptosis is a potential therapeutic target for various lung diseases, such as acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection and asthma ( Table 1 ). In this review, we summarize the association between ferroptosis and diverse lung diseases.…”

Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

“…reducing the accumulation of ROS and thus the occurrence of ferroptosis. It has been reported that ferroptosis can be initiated both by direct inhibition of GPX4, and an essential intracellular antioxidant, GSH, which are the crucial proteins in glutaminolysis (Wu et al, 2021). When ferroptosis was first defined, it was induced by erastin which inhibited cystine uptake by the cystine/glutamate antiporter, leading to suppressed antioxidant defenses due to GSH reduction (Dixon et al, 2012).…”

“…Recently, several studies have indicated that ferroptosis contributes to the stress-induced deaths of cardiac and vascular cells ( Gao et al, 2015 ; Fang et al, 2019 ; Wang and Tang, 2019 ). It has been pointed out that targeting ferroptosis can serve as a feasible approach for preventing cardiomyocyte death and managing cardiac pathologies ( Ravingerová et al, 2020 ; Wu et al, 2021 ). In this review, we will describe the mechanism of ferroptosis and discuss the role of ferroptosis in the treatment of CVDs, thereby providing a novel therapeutic strategy for CVDs in the future.…”

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

“…Existing evidence proves that ferroptosis plays an important role in the development of many diseases (7,8), such as cancer, neurodegenerative diseases, ischemia/reperfusion injury, acute kidney injury, atherosclerosis, chronic obstructive pulmonary disease, and immune system diseases. Therefore, as an evolutionary program offers various druggable nodes, ferroptosis is supposed to be an emerging way to cure many kinds of diseases (9)(10)(11)(12)(13)(14). Especially as a therapeutic model in cancer treatment and prevention of ischemic organ damage, ferroptosis has been convincingly established (15).…”