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.