Microfilaments and microtubules maintain endothelial integrity

The endothelium is a highly metabolic monolayer of cells regulating numerous physiological and pathological functions that maintain the permeability and thromboresistant functions of the endothelium. The structure and function of the endothelial cytoskeleton prevents vascular disease by regulating the structure of the endothelium to act as a resting molecular barrier to atherogenic proteins and by becoming an activated layer of migrating cells to repair denuding injuries. The purpose of this review is to examine the structure of the endothelial cytoskeleton and its roles in cell-cell and cell-substratum adhesion, cell signaling, and regulation of wound repair. Studies focused on the cellular and molecular biology of the structure and function of the endothelial cytoskeleton and in wound repair are reviewed. The cytoskeleton is a key regulator in maintaining endothelial integrity and in restoring integrity following injurious denudation, such as those that occur in the pathogenesis of atherosclerosis. Actin microfilaments and their associated adherens junctions and focal adhesions are important regulators of cell signaling, cell locomotion, cell adhesion, and wound repair mechanisms. Various proteins have been implicated in controlling cytoskeletal-based endothelial function and repair such as tyrosine kinases/phosphatases and the Rho family of proteins. The normal function of the endothelium is highly dependent on the endothelial cytoskeleton. Disruption and dysfunction of the cytoskeleton may result in impairment of endothelial function, subsequently tipping the balance towards vascular disease. Thus, an understanding of the cellular and molecular biology of the endothelial cytoskeleton is essential in our understanding of the pathogenesis of vascular disease, especially atherosclerosis.