Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method
File(s)
Published version
Author(s)
Warboys, Christina M
Ghim, Mean
Weinberg, Peter D
Type
Journal Article
Abstract
A striking feature of atherosclerosis is its highly non-uniform distribution within the arterial tree. This has been attributed to variation in the haemodynamic wall shear stress (WSS) experienced by endothelial cells, but the WSS characteristics that are important and the mechanisms by which they lead to disease remain subjects of intensive investigation despite decades of research. In vivo evidence suggests that multidirectional WSS is highly atherogenic. This possibility is increasingly being studied by culturing endothelial cells in wells that are swirled on an orbital shaker. The method is simple and cost effective, has high throughput and permits chronic exposure, but interpretation of the results can be difficult because the fluid mechanics are complex; hitherto, their description has largely been restricted to the engineering literature. Here we review the findings of such studies, which indicate that putatively atherogenic flow characteristics occur at the centre of the well whilst atheroprotective ones occur towards the edge, and we describe simple mathematical methods for choosing experimental variables that avoid resonance, wave breaking and uncovering of the cells. We additionally summarise a large number of studies showing that endothelium cultured at the centre of the well expresses more pro-inflammatory and fewer homeostatic genes, has higher permeability, proliferation, apoptosis and senescence, and shows more endothelial-to-mesenchymal transition than endothelium at the edge. This simple method, when correctly interpreted, has the potential to greatly increase our understanding of the homeostatic and pathogenic mechanobiology of endothelial cells and may help identify new therapeutic targets in vascular disease.
Date Issued
2019-06-01
Date Acceptance
2019-04-04
Citation
Atherosclerosis, 2019, 285, pp.170-177
ISSN
0021-9150
Publisher
Elsevier
Start Page
170
End Page
177
Journal / Book Title
Atherosclerosis
Volume
285
Copyright Statement
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Sponsor
British Heart Foundation
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000468732700022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
FS/16/2/31739
PG/15/102/31890
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Cardiovascular System & Cardiology
Hemodynamics
Endothelium
Mechanotransduction
Inflammation
Signalling
Model
MUSCLE-CELL PROLIFERATION
OSCILLATORY SHEAR-STRESS
MESENCHYMAL TRANSITION
FLOW DIRECTION
PERMEABILITY
RESPONSES
EXPRESSION
KINASE
GROWTH
MODEL
Publication Status
Published
Date Publish Online
2019-04-09