Laminar Shear Stress

Abstract

Abstract-Mechanical forces are important modulators of cellular function in many tissues and are particularly important in the cardiovascular system. The endothelium, by virtue of its unique location in the vessel wall, responds rapidly and sensitively to the mechanical conditions created by blood flow and the cardiac cycle. In this study, we examine data which suggest that steady laminar shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. We explore the ability of shear stress to modulate atherogenesis via its effects on endothelial-mediated alterations in coagulation, leukocyte and monocyte migration, smooth muscle growth, lipoprotein uptake and metabolism, and endothelial cell survival. We also propose a model of signal transduction for the endothelial cell response to shear stress including possible mechanotransducers (integrins, caveolae, ion channels, and G proteins N umerous studies suggest that normal functioning of the endothelium is critical in limiting the development of atherosclerosis, as illustrated by the correlation between risk factors for atherosclerosis (smoking, high cholesterol, high homocysteine, decreased estrogen, increasing age, and hypertension) and endothelial dysfunction.1 Endothelial cells play a critical role in vascular homeostasis by performing many functions. They sense and integrate hemodynamic and hormonal stimuli and effect alterations in vascular function through the secretion of various mediator proteins and molecules.2 As a result of these properties, endothelial cells modulate biological processes related to the blood vessel wall, including regulation of the permeability of plasma lipoproteins, adhesion of leukocytes, and release of prothrombotic and antithrombotic factors, growth factors, and vasoactive substances.3 Impairment of these endothelial cell-mediated processes has been postulated to play a central role in the pathogenesis of atherosclerosis. 1Just as other tissues have developed mechanisms to detect changes in the physiological conditions to which they are exposed, endothelial cells respond not only to humoral factors in the circulation but also to the mechanical conditions created by blood flow and the cardiac cycle. 4 As a result of their unique location, endothelial cells experience three primary mechanical forces: pressure, created by the hydrostatic forces of blood within the blood vessel; circumferential stretch or tension, created as a result of defined intercellular connections between the endothelial cells that exert longitudinal forces on the cell during vasomotion; and shear stress, the dragging frictional force created by blood flow. Of these forces, shear stress appears to be a particularly important hemodynamic force because it stimulates the release of vasoactive substances and changes gene expression, cell metabolism, and cell morphology. 4 The nature and magnitude of shear stress plays an important role in long-term maintenance of the structure and function of the blood vessel. T...

Endothelial cell functions

“…In contrast to the specific activation of membrane receptors by chemical ligands, mechanical forces such as shear stress activate simultaneously many membrane proteins including receptors (integrins, G-coupled receptors, and/or integral proteins within specialized membrane microdomains like caveolae) and mechanosensitive ion channels, via conformational changes or clustering, leading to the initiation of signal transduction (Traub and Berk, 1998;Jalali et al, 2001). However, the downstream signaling events remain to be elucidated.…”

Atherosclerosis and calcium signalling in endothelial cells

“…It has become increasingly recognised that the endothelium is not simply a passive barrier, but plays a crucial role in maintaining vascular homeostasis and regulating the passage of materials between the blood and the vessel wall (Traub and Berk, 1998). EC are sensitive to mechanical stimuli such as wall shear stress, as well as biochemical stimuli such as bloodborne agonists.…”

“…Endothelial turnover and permeability are increased, resulting in enhanced transmission of atherogenic matter into the intima and thus increasing likelihood of IH (Traub and Berk, 1998). Synthesis of NO is reduced, whilst expression of vasoconstrictors and mitogenic factors, such as endothelin and platelet-derived growth factor, are upregulated, increasing the rate of SMC proliferation and protein synthesis in the intima, which accelerates the process of plaque formation (Malek et al, 1999).…”

Combined effects of physiologically relevant disturbed wall shear stress and glycated albumin on endothelial cell functions associated with inflammation, thrombosis and cytoskeletal dynamics

“…Previously, it has been reported that AGEs can mediate an enhancement of ICAM‐1 expression both in vivo and in vitro 4. Furthermore, ICAM‐1 expression has been shown to be sensitive to shear stress in vitro 9, and in vivo ICAM‐1 expression is most pronounced at locations of disturbed wall shear stress20. Our findings are in agreement with these studies, and suggest that the presence of irreversibly glycated albumin during disturbed shear stress enhances EC inflammatory potential, which is a hallmark of CVDs.…”

“…The nature of the shear stress plays a pivotal role in controlling EC functions, such as inflammation, thrombosis, cytoskeletal dynamics, gap junction formation (connexin‐43 and caveolin‐1) and angiogenic potential (caveolin‐1)8. Laminar unidirectional shear stress (1–1.5 Pa) is atheroprotective9, whereas disturbed wall shear stress (elevated magnitude, low mean oscillatory or recirculation) promotes an atherogenic phenotype10. It has been reported that elevated, low mean oscillatory and recirculation shear upregulate pro‐inflammatory and pro‐thrombotic markers11, along with disrupting cytoskeletal organization.…”