Impact of Low Shear Stress Preconditioning on Endothelial Cell Traction and Alignment in Response to High Shear Stress

Fluid shear stress (FSS) plays a vital role in endothelial cell (EC) function, impacting vascular health. Low FSS triggers an inflammatory, atheroprone EC phenotype, while high FSS promotes atheroprotective responses. Yet, the adaptation of ECs to high FSS following low FSS exposure remains poorly understood. We explored this process’s influence on vascular tension by measuring traction in human umbilical vein endothelial cells (HUVECs) subjected to high FSS (1 Pa) after prior low FSS exposure (0.1 Pa). We discovered that HUVECs experienced an immediate traction increase after low FSS exposure. Intriguingly, the transition to high FSS did not further enhance traction; instead, a secondary traction rise emerged after 2 hours under high FSS, lasting over 10 hours before gradually diminishing. Conversely, HUVECs exposed directly to high FSS displayed an initial traction surge within 30 minutes, followed by a rapid decline within an hour, falling below initial levels. Notably, even after more than 20 hours of exposure to high FSS, HUVECs previously preconditioned with 1-hour of low FSS exhibited traction alignment perpendicular to the flow direction, whereas those directly exposed to high FSS displayed alignment with the flow direction, both in the short and long terms. Collectively, these results suggest that even brief exposure to low FSS can initiate a low-shear-sensitive response in ECs, which requires a much-extended period to recover towards tension relaxation under laminar high shear flow conditions.