Effect of flow on the process of endothelial cell division.

Abstract

In this study we investigated the effect of flow and the associated shear stress on the process of endothelial cell division. A shear stress of 7 N/m 2 (70 dyne/cm 2 ) was applied to a monolayer of bovine aortic endothelial cells (BAECs) by using a parallel-plate flow-chamber system. Dividing cells under flow conditions were qualitatively compared with those under static-culture conditions. In addition, the duration of some phases of the cell cycle (ie, mitosis and cytokinesis) was measured for both static and flow conditions. Dividing BAECs in static cultures bowed upward; however, when cells were preconditioned by at least 6 hours of exposure to flow, they stayed relatively attached to the substrate during the entire V ascular endothelial cells (ECs) line the inside of blood vessels and the chambers of the heart. The endothelium, a selective barrier between blood components and the vessel wall, interacts actively with both of them.1 ECs also secrete vasoactive substances (eg, histamine, prostacyclin, and endotheliumderived relaxing factor) and extracellular matrix proteins (eg, fibronectin and glycosaminoglycans).The role that the endothelium plays in the genesis of atherosclerosis has also been recognized.2 Initiating events include intimal smooth muscle cell (SMC) migration and proliferation; synthesis and deposition by SMCs of connective tissue matrix proteins, including collagen, elastin fibers, and proteoglycans; and accumulation of lipids within proliferating SMCs and macrophages, which become foam cells, as well as newly formed connective tissue matrix. In the early stages of atherosclerotic disease, the endothelium is intact but is believed to be a mediator of effects associated with blood flowing through a vessel. This includes hemodynamic effects. It has been shown that hemodynamic features and lesion location are correlated, with the location of atheromas usually at sites where shear stress is low and oscillates with a high residence time.3 Several studies have shown that endothelial morphology is an indicator of the pattern of blood flow. 46In vivo permeability experiments with Evans blue dye have shown that ECs are more permeable to macromolecules at sites that are prone to the formation of atherosclerotic lesions.710 These so-called "blue sites" appear to be correlated with an increased rate of EC proliferation; ie, the "leaky" cells appear to be ECs that are undergoing cell division.11 ' 12Received August 10, 1993; revision accepted January 25, 1994. From the Biomechanics Laboratory and School of Mechanical Engineering, Georgia Institute of Technology, Atlanta.Correspondence to Robert M. Nerem, Biomechanics Laboratory and School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0405. process of cell division. Cell area significantly decreased during division for both static-culture and flow conditions. Finally, although significant changes in the duration of phases were observed in single experiments during which cells were exposed to shear stress, any differ...

Proatherogenic Flow Conditions Initiate Endothelial Apoptosis via Thrombospondin-1 and the Integrin-Associated Protein

“…The onset of apoptosis due to flow disturbances may constitute the leading stimulus in initiation of atherosclerosis. It has also been shown that the nature of hemodynamic flow influences the proliferative status of vascular endothelium (19). There are numerous descriptions of atherosclerotic lesions in areas of disturbed flow (17, 18, 20 -24, 24 -28).…”

In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

“…Furthermore, this nonphysiological culture condition may accelerate endothelial dedifferentiation and further enhance the loss of the BBB characteristics with serial cell passage (e.g., cellular polarity determined by the functional specialization of the apical and basolateral membranes) 57. The lack of antimitotic influences by laminin and flow shorten the life span of the endothelium and cause ECs to grow uncontrolled in a multilayer fashion141,142 when cells start dedifferentiating. ECs grown in Transwell tend to have irregular patterns of cell adhesion, which prompt the so‐called “edge effect.” This term refers to a condition wherein the inability to form proper tight junctions between adjacent cells and between the endothelium alongside the perimeter of the membrane and the inner wall of the luminal chamber leads to artifactual paracellular diffusion, thus affecting the reliability of permeability measurements across the endothelial monolayer.…”

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

“…The mechanotransduction effects of shear stress are believed to mediate several cellular functions, including the inhibition of cellular proliferation by the activation of p53 expression with the potential of arresting endothelial cell apoptosis . Furthermore, in the absence of laminar flow, static monolayers can be subject to uncontrolled growth, resulting in formation of multiple layers, if allowed to proliferate . Therefore, a model with the ability to incorporate physiologically relevant shear stresses is essential to effectively capture biologically relevant transport across any barrier in direct contact with the bloodstream.…”

“…46 Furthermore, in the absence of laminar flow, static monolayers can be subject to uncontrolled growth, resulting in formation of multiple layers, if allowed to proliferate. 47 Therefore, a model with the ability to incorporate physiologically relevant shear stresses is essential to effectively capture biologically relevant transport across any barrier in direct contact with the bloodstream. Additional limitations of existing models to probe human brain permeability include the use of rodent brain endothelial cells, 36,40 which do not exhibit the same anatomical and molecular complexities as their human counterparts.…”