Mij
Senior Member (Voting Rights)
Significance
Mechanical cues such as shear stress, matrix stiffness, and cyclic stretch critically regulate NET formation, yet their role in neutrophil-driven inflammation remains underexplored. Understanding how biomechanical forces modulate NETosis offers new insight into immune dysregulation in aging, atherosclerosis, and thrombosis. This perspective highlights emerging mechanobiological pathways as potential therapeutic targets, enabling the immunology field to tackle inflammation without compromising host defense.Highlights
Neutrophil extracellular traps (NETs) act as a double-edged sword: while essential in infection control and wound healing, excessive NETosis drives chronic inflammation and tissue damage.Mounting evidence links dysregulated NET formation to cardiovascular diseases and thrombotic events.
Emerging data suggest mechanical cues and cellular stress as potent, non-infectious triggers of NETosis, expanding our understanding beyond classical pathogen-driven activation.
These advances position NETs at the intersection of host defense and disease, motivating renewed interest in their therapeutic targeting.
Abstract
Neutrophil extracellular trap (NET) formation, or NETosis, is a key innate immune response that contributes to cardiovascular diseases, including vascular inflammation, atherosclerosis, and thrombosis. In the cardiovascular system, neutrophils encounter mechanical cues such as shear stress, matrix stiffness, and cyclic stretch that influence their activation and NET release. This review examines emerging evidence linking altered mechanotransduction to dysregulated NETosis in vascular aging and cardiovascular pathology. We also highlight intracellular signalling pathways by which neutrophils sense and respond to mechanical stress. Understanding how biomechanical cues regulate NETosis may uncover novel therapeutic opportunities to control inflammation in cardiovascular disease without compromising host defense.LINK