Haoxiu Li 1†and Meng Bi 1†contributed equally to this work and share first authorship.
Abstract: Ferroptosis is a new non-apoptotic form of regulatory cell death, which is characterized by intracellular iron overload and excessive accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis is closely related to intracellular iron, amino acid, and lipid metabolism disorders. Ferroptosis is increasingly recognized as an important process mediating the pathogenesis and progression of acute ischemic stroke, and it can be involved in influencing acute ischemic stroke and acute ischemic stroke risk factors atherosclerosis, atrial fibrillation, hypertension, diabetes mellitus, and obstructive sleep apnea. Therefore, understanding the mechanisms of ferroptosis regulation in different diseases may have significant implications for the preventive treatment and improvement of prognosis in patients with acute ischemic stroke and patients with risk factors for acute ischemic stroke. This article reviews not only the specific important mechanisms of ferroptosis in the development of acute ischemic stroke, but also the relevant associations between risk factors for acute ischemic stroke and ferroptosis, and describes the current limitations and future directions of ferroptosis in the pathogenesis of acute ischemic stroke and its risk factors.
Keywords: Ferroptosis, Acute ischemic stroke, Atherosclerosis, Atrial fibrillation,Hypertension.
Introduction
Acute ischemic stroke (AIS) is a disease caused by the insufficient blood supply to the brain resulting in neuronal necrosis and brain dysfunction, and is one of the leading causes of death and disability, affecting millions of people worldwide1. Ferroptosis is a new form of non-apoptotic cell death first proposed by Dixon in 2012, which is characterized by intracellular iron overload and excessive accumulation of lipid peroxides and reactive oxygen species (ROS), and its occurrence is related to the three major metabolic disorders of intracellular iron, amino acid, and lipid2,3. In recent years, more and more studies have shown that ferroptosis is not only involved in the development of AIS but also in the development of AIS risk factors such as atherosclerosis, atrial fibrillation, hypertension, diabetes mellitus, obstructive sleep apnea, and so on4-9. The use of ferroptosis inhibitors such as ferrostatin-1 and deferoxamine can not only prevent neuronal cell death and reduce secondary brain injury after stroke to improve the prognosis of patients but also slow the pathological progression of AIS risk factors8,10-14, which suggests that regulating ferroptosis may become a new method for the prevention and treatment of AIS. This article mainly reviews the research progress of the mechanism of ferroptosis in AIS and its risk factor-related diseases, and by understanding the specific mechanism of ferroptosis in stroke and its risk factor-related diseases, it is expected to provide a reference for the prevention and treatment of acute ischemic stroke by targeting ferroptosis, to significantly improve the prognosis and survival of patients.