(B-78) Vascular Smooth Muscle Cell Orientation Induced by Cocultured Endothelial Cells Subjected to Wall Shear Stress

Introduction:: Vascular smooth muscle cells (SMCs) communicate with vascular endothelial cells (ECs) through bioactive factors and change their morphology and functions. SMCs play an important role in vascular physiology and pathology including angiogenesis, vascular remodeling, and vascular tonus. These SMC functions are influenced by hemodynamic stimuli, including wall shear stress (WSS), through interactions with ECs directly subjected to. However, details of EC-SMC interaction and responses of SMCs under WSS conditions remain to be elucidated. In this study, we investigated the effects of interaction with ECs under a WSS condition on the morphology of SMCs.


Materials and Methods:: An EC-SMC coculture model constructed with centrifugally compressed cell–collagen combined construct (C6) was used in this study. A type I collagen gel in which human aortic SMCs were embedded was compressed by a 1,000 g centrifugal force with a plate centrifuge for 10 min. After 6-7 days of static culture, human aortic ECs were seeded on the compressed gel (C6). The EC-SMC coculture was statically cultured further for 1-2 days and then was exposed to 2 Pa steady WSS, assumed as a physiological condition for 24 h. A SMC model, constructed of only C6 without ECs, was also exposed to the WSS. ECs and SMCs after the WSS exposure were observed with fluorescent microscopy for morphological analysis.

Results, Conclusions, and Discussions:: In the SMC models, only SMCs that resided near the surface of the C6 and may be contacted with the flow tended to align with the direction of the flow after 24h of WSS exposure, while those in bottom layer did not show orientation in any specific direction. In the coculture models, ECs on the surface of the C6 aligned with the flow, and SMCs below ECs, not directly exposed to the flow, orientated perpendicularly to the flow direction regardless of their position in the C6. Since the perpendicular orientation of SMCs to the direction of the flow only occurred in the EC-SMC coculture models, and SMCs were not directly exposed to the flow, WSS related-signaling transduced by ECs are supposed to cause this SMCs orientation. The underlying mechanisms remain unclear, but our results suggest that SMCs which indirectly contact with flow can sense WSS environments, including the flow direction, through ECs, and the EC-SMC interactions may be important for a better understanding of vascular pathophysiology.


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