Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

Abstract

The effects of hemodynamic forces upon vascular endothelial cell turnover were studied by exposing contact-inhibited confluent cell monolayers to shear stresses of varying amplitude in either laminar or turbulent flow. Laminar shear stresses (range, 8-15 dynes/cm2; 24 hr) induced cell alignment in the direction of flow without initiating the cell cycle. In contrast, turbulent shear stresses as low as 1.5 dynes/cm2 for as short a period as 3 hr stimulated substantial endothelial DNA synthesis in the absence of cell alignment, discernible cell retraction, or cell loss. The results of these in vitro experiments suggest that in atherosclerotic lesion-prone regions of the vascular system, unsteady blood flow characteristics, rather than the magnitude ofwall shear stressperse, may be the major determinant of hemodynamically induced endothelial cell turnover.Hemodynamic forces have been implicated in the initiation, localization, and development of atherosclerotic vascular disease (1, 2). Little is known, however, about the effects of such forces upon the endothelial cell lining of blood vessels, the integrity of which is essential for normal vascular function. In certain areas ofthe aorta and its main branches, blood flow characteristics are both variable and complex. In locations such as the descending thoracic aorta and distal carotid arteries, pulsatile laminar flow is prevalent (3), whereas in other regions, such as coronary arteries and the carotid bifurcation, secondary flows, vortices, and intermittently changing flow directions are encountered (4). The distribution of atherosclerotic lesions in susceptible species, including humans, is closely correlated with the location of disturbed flow in the major vessels (5). Time-dependent flow separation and unsteady secondary flow typically occur in localized regions that are usually well defined and of limited size. Furthermore, turbulence will occur in the largest arteries under conditions of increased flow velocity and cardiac output (4). Thus, shear stresses, which are the direct tractive forces acting on the endothelial cell surface as a result of blood flow, are highly variable in magnitude, frequency, and direction in such regions.Autoradiographic studies in vivo have demonstrated increased endothelial DNA synthesis in localized areas of the aorta and its major branches, suggesting that locally increased endothelial cell turnover, perhaps as a result of injury, may occur near branches and bifurcations (6, 7). Increased cell turnover need not imply denudation of the endothelium and indeed during the initiation and early development of atherosclerotic lesions the endothelium remains a confluent monolayer of cells (8).The role of fluid shear stress in promoting endothelial cell injury and/or turnover is uncertain: both high and low shear stresses have been implicated. High shear stress has been linked to alignment of endothelial cells (9), cell loss (10), increased arterial permeability (11), and enhanced endothelial biosynthetic capabilities (12). Ath...

The effects of shear flow on protein structure and function

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Assessment of turbulent flow effects on the vessel wall using four-dimensional flow MRI

“…Of particular interest as disease predictors and descriptors are areas of turbulent flow and their effects on the vessel walls. Turbulent flow near the vessel wall has been associated with adverse vascular remodelling, and damage to the vessel wall (3)(4)(5)(6)(7)(8)(9)(10)). …”

“…In a region with steady and laminar flow, endothelial cells align along the direction of flow (6). In contrast, turbulent flow fails to align the cells, presumably because the direction, magnitude, and frequency of the shear and pressure stresses are chaotic (6,7). These unaligned cells appear to lose much of their athero-protective capabilities.…”

Force-induced focal adhesion translocation: effects of force amplitude and frequency

“…Cells exposed to rapidly fluctuating shear stress environments, generated with turbulent flow, do not align with the direction of flow as do cells exposed to laminar fluid shear stress (10), whereas oscillating fluid shear stress with a low mean positive force does not induce the same gene expression as flow with a high mean positive force (15,18,44). Furthermore, ramped levels of laminar fluid shear stress result in graded nitric oxide (29) and intracellular calcium (38) responses.…”