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(Circulation Research. 2006;98:939.)
© 2006 American Heart Association, Inc.

Cellular Biology

Shear Stress Regulates Forward and Reverse Planar Cell Polarity of Vascular Endothelium In Vivo and In Vitro

Shannon McCue, Dorota Dajnowiec, Feng Xu, Ming Zhang, Moira R. Jackson, B. Lowell Langille

From the Department of Laboratory Medicine and Pathobiology (S.M., D.D., B.L.L.), University of Toronto, Canada; Toronto General Research Institute (S.M., D.D., F.X., M.Z., B.L.L.), University Health Network, Canada; and Department of Anatomy and Cell Biology (M.R.J.), College of Medicine, University of Florida, Gainesville.

Correspondence to B. Lowell Langille, PhD, MaRS Centre, Toronto Medical Discoveries Tower, 101 College St, 3-308, Toronto, ON, M5G 1L7, Canada. E-mail langille{at}uhnres.utoronto.ca

Cultured vascular endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferred. The regulation of endothelial PCP is therefore controversial. We report that the direction of PCP in blood vessels is age and vessel specific; nonetheless, it is caused by shear-related regulation of glycogen synthase kinase-3ß (GSK-3ß), a profound regulator of endothelial microtubule stability. When GSK-3ß is inhibited, PCP reverses direction. Endothelium is the only cell type studied to date that can reverse direction of polarity. Tight regulation of GSK-3ß, microtubule dynamics, and cell polarity was also required for the striking morphological responses of endothelium to shear stress (cell elongation and orientation with shear). Finally, the cytoskeletal polarity displayed in blood vessels is associated with polarized (shear-directed) cell mitoses that have important effects on endothelial repair. Vascular endothelium therefore displays a novel mode of mechanosensitive PCP that represents the first example of a single cell type that can reverse direction of polarity.

Key Words: shear stress • endothelium • microtubules • planar cell polarity

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Mechanical and Chemical Regulation of Endothelial Cell Polarity

Shu Chien
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