The role of microtubules in endothelial cell adaptation to shear stress.
Published: 2006
Language: eng
Number of pages: 173
ISBN-13: 9780494219102
Description: Shear stress, the fictional force of blood flow, affects the structure of blood vessels, for example, an increase in flow leads to an increase in vessel diameter. Cellular remodeling also occurs in the endothelium; the monolayer of cells that line the inner surface of the vessel wall and are constantly in contact with the blood. In straight areas of vessels where flow is laminar the endothelial cells are elongated but at curves and bifurcations flow is complex. Alterations in blood flow cause the endothelium to morphologically adapt by remodeling the cell-cell and cell-substrate adhesions, and the cytoskeleton.This thesis examined the role of microtubules, a component of the cytoskeleton, in adaptations of vascular endothelium to shear stress. In sheared endothelial cultures, the cells become elongated and aligned in the direction of flow and are polarized. The adhesion complexes and cytoskeleton are reorganized, but how this process occurs is unknown. My results demonstrate that shear stress-induced polarization of the endothelium is via a tightly controlled process that is regulated by microtubule dynamics and the enzyme GSK-3beta. Furthermore, the actin cytoskeleton and the motor protein, kinesin, are critical for endothelial cells to change shape. Microfilaments guide dynamic microtubules to the poles of the cells, and kinesin, associated with stable microtubules, transports intracellular proteins to the cell cortex. Understanding the process of how endothelial cells adapt to alterations in blood flow, will provide important insights into both endothelial cell biology and the general control of cell motility.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0041.

Thesis (Ph.D.)--University of Toronto, 2006.

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