Multiscale modeling reveals non-linear dynamics of AKT-mediated NO-ROS crosstalk in shear stress-induced endothelial phenotype.

Multiscale modeling shows that endothelial repair under shear stress depends on nonlinear AKT/NO/ROS interactions, with a critical intervention window on Day 1.

• Why it matters: Understanding how AKT signaling influences endothelial repair is vital for developing targeted therapies for atherosclerosis, yet the complex regulation remains unclear.
• What they did: A multiscale model integrating hemodynamics, cellular behavior, and biochemical kinetics was developed to simulate endothelial phenotypic transitions and redox dynamics, revealing key nonlinear interactions.
• The result: Findings indicate that timely moderate AKT activation can restore endothelial function by maintaining redox balance, while excessive activation causes over-suppression, emphasizing the importance of intervention timing and dosage.