Role of cytoskeletal alignment, independent of fluid shear stress, in endothelial cell functions

Atherosclerosis is closely linked to endothelial cell (EC) function, which is strongly influenced by fluid shear stress (FSS). While high, unidirectional FSS produces elongated, aligned ECs with athero‑protective behaviors, low or oscillatory FSS results in cobblestone‑shaped ECs that promote an athero‑prone environment. Whether EC shape itself, independent of FSS, regulates EC function is not well understood. Using micropatterned protein lanes to induce EC elongation without flow, this study shows that elongated EC shape and cytoskeletal alignment reproduce several protective functional characteristics, including extracellular matrix deposition, reduced inflammation, and lower thrombotic potential. These findings suggest that cytoskeletal organization actively contributes to EC functions that support cardiovascular health, independent of mechanical shear forces.