MECHANISM OF MORPHOLOGICAL CHANGES IN ENDOTHELIAL CELLS UNDER FLUID SHEAR STRESS WITH ITS SPATIAL GRADIENT
Daisuke Yoshino1, Naoya Sakamoto2, Masaaki Sato3
1Institute of Fluid Science, Tohoku University, Japan;
2Tokyo Metropolitan University, Japan;
3Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Japan
Cerebral aneurysms are pathologic dilations of arterial walls that frequently occur around arterial bifurcations. Since local hemodynamics at such sites is complex, high shear stress (SS), and high shear stress gradient (SSG), it has been suggested that the unique hemodynamic conditions play a key role in pathology of aneurysm. Endothelial cells (ECs), lining on the luminal wall of blood vessels, are linked to the maintenance or breakdown of vascular homeostasis functions due to hemodynamic stimuli. Although the bulk of literatures have shown that ECs elongate and align to the direction of flow after exposure to physiological levels of SS, knowledge of morphological responses of ECs to combination of SS and SSG is still limited. In this study, we demonstrated vascular ECs exhibited morphological responses depending on magnitude relationship between SS and SSG. Although ECs exposed to lower SS with SSG were not oriented and were elongated to the flow direction, they started to exhibit orientation, elongation, and development of actin stress fibers, even under the condition of SS with SSG when SS exceeded a certain value. We also estimated strain field in ECs exposed to SS with/without SSG using a simple mechanical model. For the condition of laminar SS, tensile and compressive strains were distributed in upstream and
downstream sides, respectively, of cell-cell border. In contrast, tensile strain was distributed in both sides of the border for the condition of SS with SSG. Less difference in magnitude of the strain between upstream and downstream sides of cell-cell border was also observed under the low SS conditions with SSG. We showed localization of a protein associated with SS mechano-sensing, corresponding to the estimated strain fields. Based on the results of this study, we finally suggested a mechanism of morphological changes in ECs under SS with SSG.