Response of vascular endothelial cells to fluid flow.

KEIGI FUJIWARA, MICHITAKA MASUDA, MASAKI OSAWA, KAZUO KATOH, YUMIKO KANO, NOBORU HARADA, AND ROSANGELA B. LOPES Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, 56.54565 Japan Fluid flow triggers a variety of responses in vascular endothelial cells (ECs), such as initiation of signal trans- duction, modulation of gene expression, and remodeling of cytoskeletal and related structures. However, the pri- mary steps of mechanosensing are not known. Because fluid flow is a mechanical (thus vectorial) stimulus, we decided to study how ECs respond in a vectorial manner. Among the various types of responses (for review, see Davies, 1995), those involving the cytoskeleton are clearly vectorial. Using a parallel plate flow chamber mounted on a light microscope, we first analyzed morphological responses of ECs to laminar flow (Masuda and Fujiwara, 1993a, b). We found that, in addition to the already known morpho- logical responses of ECs to flow (i.e., the elongation and alignment of ECs parallel to the direction of flow and alignment of stress fibers in the flow direction), flow in- duced preferential development of lamellipodia in the di- rection of flow. This latter response caused ECs to migrate preferentially in the flow direction. Although it takes many hours for both the cell shape change and the align- ment responses to become recognizable, the motility pat- tern change was detectable in 5 - 10 min. This is the fastest morphology-related response of ECs exposed to flow. ECs exhibit little morphologically detectable responses when exposed to fluid shear stress of less than 0.4 Pa (4 dyn/cm2), although it is known that many signal-transduc-