Ischemia - Reperfusion injury: A roadmap to precision therapies

Abstract

Ischemia-reperfusion (I/R) injury is prevalent in the medical field and significantly limits the therapeutic outcomes of various ischemic diseases, adversely affecting patient prognosis. The pathogenesis of I/R injury is highly complex, involving intricate interactions among oxidative stress, inflammatory responses, mitochondrial dysfunction, and multiple cell death pathways. Once the mitochondrial respiratory chain is impaired, it triggers oxidative stress responses, leading to the excessive production of reactive oxygen species (ROS). Excessive ROS not only directly damage cells but also activate inflammatory responses and initiate multiple cell death signalling pathways, such as necroptosis, pyroptosis, and ferroptosis, thereby exacerbating tissue damage. Moreover, the clinical manifestations of I/R injury vary significantly across different organs, such as the heart, brain, kidneys, liver, and lungs, and are further influenced by patients' underlying conditions, posing challenges for clinical diagnosis and treatment. Therefore, constructing a comprehensive assessment system based on individual patient characteristics (such as genetic polymorphisms and comorbidities) to accurately predict the risk of I/R injury is particularly important. Currently, there are diverse strategies for the prevention and treatment of I/R injury, but translating basic research into clinical application remains challenging. Developing personalized treatment plans tailored to different cell types holds promise for overcoming existing therapeutic bottlenecks, significantly improving patient outcomes, and providing new directions for addressing the challenges of I/R injury.