S1P in the development of atherosclerosis: roles of haemodynamic wall shear stress and endothelial permeability
File(s)
Accepted version
Author(s)
Weinberg, Peter
Warboys, Christina M
Type
Journal Article
Abstract
Atherosclerosis is characterised by focal accumulations of lipid within the arterial wall, thought to arise from effects of haemodynamic wall shear stress (WSS) on endothelial permeability. Identifying pathways that mediate effects of shear on permeability could therefore provide new therapeutic opportunities. Here we consider whether the sphingosine-1-phosphate (S1P) pathway could constitute such a route. We review effects of S1P in endothelial barrier function, the influence of WSS on S1P production and signalling, the results of trials investigating S1P in experimental atherosclerosis in mice, and associations between S1P levels and cardiovascular disease in humans. Although it seems clear that S1P reduces endothelial permeability and responds to WSS, the evidence that it influences atherosclerosis is equivocal. The effects of specifically pro- and anti-atherosclerotic WSS profiles on the S1P pathway require investigation, as do influences of S1P on the vesicular pathways likely to dominate low density lipoprotein transport across endothelium.
Date Issued
2021-09-18
Date Acceptance
2021-07-19
Citation
Tissue Barriers, 2021, 9 (4), pp.1-18
ISSN
2168-8362
Publisher
Taylor and Francis
Start Page
1
End Page
18
Journal / Book Title
Tissue Barriers
Volume
9
Issue
4
Sponsor
British Heart Foundation
Identifier
https://www.tandfonline.com/doi/full/10.1080/21688370.2021.1959243
Grant Number
FS/16/2/31739
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Coronary artery disease
cytoskeleton
mechanosensor
sphingosine-1-phosphate receptor
transverse wall shear stress
LOW-DENSITY-LIPOPROTEIN
RABBIT AORTIC-WALL
PLASMA SPHINGOSINE-1-PHOSPHATE CONCENTRATION
SPHINGOSINE 1-PHOSPHATE
BARRIER ENHANCEMENT
ARTERIAL-WALL
AMELIORATES ATHEROSCLEROSIS
VASCULAR-PERMEABILITY
CULTURED ENDOTHELIUM
SURFACE GLYCOCALYX
Coronary artery disease
cytoskeleton
mechanosensor
sphingosine-1-phosphate receptor
transverse wall shear stress
Publication Status
Published
Date Publish Online
2021-09-18