Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells

Abstract

Vascular endothelial cells (ECs), which exist in close proximity to vascular smooth muscle cells (SMCs), are constantly subjected to blood flow-induced shear stress. Although the effect of shear stress on endothelial biology has been extensively studied, the influence of SMCs on endothelial response to shear stress remains largely unexplored. We examined the potential role of SMCs in regulating the shear stress-induced gene expression in ECs, using a parallel-plate coculture flow system in which these 2 types of cells were separated by a porous membrane. In this coculture system, SMCs tended to orient perpendicularly to the flow direction, whereas the ECs were elongated and aligned IntroductionVascular endothelial cells (ECs), which provide an interface between the blood and the vessel wall, are constantly subjected to hemodynamic forces, including the shear stress imposed by blood flow. Shear stress affects leukocyte-EC interaction and the subsequent leukocyte extravasation into inflamed tissues. 1,2 The effects of fluid shear stress on endothelial biology and gene expression have been extensively studied. [3][4][5][6][7] In addition to its physical influence on leukocyte-EC adhesion, 8,9 shear stress can alter the adhesive properties of ECs by modulating the surface expression of adhesive proteins, for example, intercellular adhesion molecule-1 (ICAM-1), 10-15 vascular cell adhesion molecule-1 (VCAM-1), 10,11,13,14,16,17 and E-selectin. 13,18 Exposure of ECs to laminar flow increases the gene and protein expression of ICAM-1. [10][11][12][13][14][15] Our recent study demonstrated that this shear flow-induced increase in ICAM-1 expression is partially due to an elevation of the levels of intracellular reactive oxygen species (ROS) in ECs. 15 In contrast to ICAM-1, shear stress treatment of ECs has only a minor effect on the surface expression of VCAM-1, or may even cause a reduction. 10,11,13,14,16,17 E-selectin has been reported to be less responsive to laminar shear stress 13 and more responsive to oscillatory flow condition. 18 Most studies on how shear stress affects ECs have been performed by using a cultured EC monolayer as an experimental model. The vessel wall is composed of several types of cells, including ECs, smooth muscle cells (SMCs), and fibroblasts. There is increasing evidence that cell-to-cell interactions can control cellular growth, migration, differentiation, and function. 19 Physical contact between ECs and SMCs via myoendothelial bridges has been demonstrated in vivo 20,21 and may play an important role in cellular communication. Hence, in vitro models for studying ECs need to simulate the in vivo environment by coculturing ECs in close proximity to SMCs. Several coculture models have recently been developed. [22][23][24][25][26] Ziegler et al 22 designed a coculture model that includes SMCs, ECs, and a matrix of collagen gel. They demonstrated that ECs cocultured with SMCs aligned with the flow direction more rapidly than ECs grown on plastic. Redmond et al 23 developed a system in whic...

Lymphocyte traffic through sinusoidal endothelial cells is regulated by hepatocytes†

“…This is supported by studies showing that increased adhesion molecule expression induced by coculturing HUVEC with smooth muscle cells was abolished when direct contact between the two cells was prevented. 45 It is also possible that activating signals that modulate the endothelial or hepatocyte phenotype are produced as a result of the close juxtaposition of cells in our coculture system. For example, it recently was demonstrated that significant synthesis of the coagulation factor FVIII by hepatocytes in culture only occurs in the presence of vWF derived from ECs.…”

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…A co-culture system was used to investigate the synergistic effects of advanced glycation end-products on intercellular-cellular interactions [93,94], creating a more realistic platform for atherosclerosis research. Chiu et al [95][96][97] developed an important EC-VSMC co-culture system in which ECs are not only in close proximity to VSMCs, but are also constantly subjected to shear stress. In this model, ECs and VSMCs are separated by a porous membrane, with only the ECs being subjected to flow conditions.…”

“…Atheroprone flow decreases VSMC gene expression (a-SMA and myocardin) and induces a proinflammatory phenotype in ECs and VSMCs by upregulating expression of VCAM-1, IL-8 and monocyte chemoattractant protein-1 (MCP-1) [111]. Shear stress downregulates pathophysiologically relevant gene expression under EC-VSMC co-culture [95,97].…”

Biomechanical Factors Analysis in Aneurysm

“…In response to reduced distal arterial resistance and increase flow, such as is demonstrated in the response to even modest lower extremity exercise, wall shear stress becomes antegrade and laminar throughout the cardiac cycle, mimicking those characteristic of more proximal aortic segments. These distinct regional differences in hemodynamic influences may account for some component of the differential aneurysm risk noted between the thoracic and abdominal aortic segments (Dua and Dalman, 2010 As commented above, there are several work in the literature that show a correlation between very low shear stresses and the loss of permeability of the endothelial cell membrane (Helmlinger et al, 1991;Chiu et al, 2003). Studies have been the basis of an alternative, or even complementary, mechanism responsible for the origin of these aneurysms.…”