Mechanosensitive reactive oxygen Species:A precision medicine target for oxidative stress-related diseases

Oxidative stress induced by abnormal mechanical stress is a common pathological mechanism underlying the initiation and progression of various injury and diseases. Mechanosensitive reactive oxygen species (mechano-ROS), a subset of ROS specifically elicited by mechanical stress, are primarily generated from distinct sources including NADPH oxidases (NOXs), mitochondrial electron transport chain (ETC), uncoupled endothelial nitric oxide synthase (eNOS), and xanthine oxidase (XO/XOR) in a disease-specific manner. These mechano-ROS act as critical signaling mediators that link aberrant mechanical cues to cellular dysfunction, inflammation, barrier disruption, and disease progression. Scavenging excessive reactive oxygen species (ROS) has thus emerged as a key strategy for mitigating injury and disease progression. However, the primary enzymatic systems and cellular sources responsible for ROS generation differ across diseases, which may partly account for the limited clinical efficacy of broad-spectrum antioxidant therapies. Consequently, targeted interventions that identify and inhibit disease-specific major ROS sources, in combination with ROS-scavenging strategies, could synergistically reduce oxidative stress by both upstream source suppression and downstream ROS clearance. This approach offers promising avenues for the precision attenuation/treatment of different injury and diseases.