The Endothelial Cytoskeleton: Organization in Normal and Regenerating Endothelium*

Abstract

The components of the endothelial cell cytoskeleton that have been shown to be important in maintaining endothelial structural integrity and in regulating endothelial repair include F-actin microfilament bundles, including stress fibers, and microtubules, and centrosomes. Endothelial cells contain peripheral and central actin microfilaments. The dense peripheral band (DPB) consists of peripheral actin microfilament bundles which are associated with vinculin adhesion plaques and are most prominent in low or no hemodynamic shear stress conditions. The central microfilaments are very prominent in areas of elevated hemodynamic shear stress. There is a redistribution of actin microfilaments characterized by a decrease of peripheral actin and an increase in central microfilaments under a variety of conditions, including exposure to thrombin, phorbol-esters, and hemodynamic shear stress. During reendothelialization, there is a sequential series of cytoskeletal changes. The DPB remains intact during the rapid lamellipodia mediated repair of very small wounds except at the base of the lamellipodia where it is splayed. The DPB is reduced or absent when cell locomotion occurs to repair a wound. In addition, when cell locomotion is required, the centrosome, in the presence of intact microtubules, redistributes to the front of the cell to establish cell polarity and acts as a modulator of the directionality of migration. This occurs prior to the loss of the DPB but does not occur in very small wounds that close without migration. Thus, the cytoskeleton is a dynamic intracellular system which regulates endothelial integrity and repair and is modulated by external stimuli that are present at the vessel wall-blood interface.