S1P in the development of atherosclerosis: roles of haemodynamic wall shear stress and endothelial permeability

Warboys, Christina M; Weinberg, Peter D

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.

Citation

Warboys, C. M., & Weinberg, P. D. (2021). S1P in the development of atherosclerosis: roles of haemodynamic wall shear stress and endothelial permeability. Tissue Barriers, https://doi.org/10.1080/21688370.2021.1959243

• Journal Article Type: Review
• Acceptance Date: Jul 19, 2021
• Publication Date: Sep 18, 2021
• Deposit Date: Jul 1, 2021
• Publicly Available Date: Sep 18, 2022
• Journal: Tissue Barriers
• Print ISSN: 2168-8362
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1080/21688370.2021.1959243
• Keywords: coronary artery disease; mechanosensor; cytoskeleton; sphingosine-1-phosphate receptor; transverse wall shear stress
• Public URL: https://rvc-repository.worktribe.com/output/1549597