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Published Online
on May 7, 2007

Hypertension. 2007
Published online before print May 7, 2007, doi: 10.1161/HYPERTENSIONAHA.107.089730
A more recent version of this article appeared on July 1, 2007
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Submitted on February 23, 2007
Revised on March 16, 2007

Force-Induced Polarized Mitosis of Endothelial and Smooth Muscle Cells in Arterial Remodeling

Dorota Dajnowiec; Peter J.B. Sabatini; Thea C. Van Rossum; Jacky T.K. Lam; Ming Zhang; Andras Kapus; and B. Lowell Langille*

From the Department of Laboratory Medicine and Pathobiology (D.D., P.J.B.S., T.C.V.R., J.T.K.L., M.Z., B.L.L.), University of Toronto, Toronto, Ontario, Canada; Toronto General Research Institute (D.D., P.J.B.S., T.C.V.R., J.T.K.L., M.Z., B.L.L.), University Health Network, Toronto, Ontario, Canada; and the Department of Surgery (A.K.), University of Toronto and St Michael’s Hospital Research Institute, Toronto, Ontario, Canada.

* To whom correspondence should be addressed. E-mail: langille{at}uhnres.utoronto.ca.

Abstract--Arteries display highly directional growth and remodeling that are specific to increases in the mechanical loads imposed on them by blood pressure, blood flow, and lengthwise tensile forces that are transmitted from the tissues to which they are attached. This study examined the effect of mechanical forces on the direction in which mitosis delivers daughter cells, as a mechanism for directional growth. Lateral forces were imposed on surface integrins of cultured endothelial cells by seeding the cells with arginine-glycine-aspartate peptide-coated magnetic microspheres and applying a magnetic field. Video images revealed that the mitotic axis of dividing cells became highly biased in the direction of applied force. Distribution of cortactin, which participates in polarized mitoses driven by other stimuli, was highly sensitive to mechanical loading and interfering with cortactin function arrested cell growth. Smooth muscle cell mitoses also proved to be sensitive to mechanical force: when lengthwise force imposed on rabbit carotid arteries was altered by excision of a vessel segment and reanastomosis of the cut ends, direction of mitosis was dramatically altered. These findings indicate that influences of mechanical force can modulate the manner in which mitosis of vascular cells contributes to reorganization of arterial wall tissue.


Key words: blood vessels • blood pressure • hyperplasia • integrins • tensile stress • remodeling • vascular diseases




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