Imperial College London
Alternate

ProfessorPeterWeinberg

Faculty of Engineering, Department of Bioengineering

Professor in Cardiovascular Mechanics
 
 
 
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Contact

 

+44 (0)20 7594 1517p.weinberg Website

 
 
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Location

 

4.10Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ghim:2021:10.1016/j.atherosclerosis.2021.08.025,
author = {Ghim, M and Pang, KT and Burnap, SA and Baig, F and Yin, X and Arshad, M and Mayr, M and Weinberg, PD},
doi = {10.1016/j.atherosclerosis.2021.08.025},
journal = {Atherosclerosis},
pages = {56--66},
title = {Endothelial cells exposed to atheroprotective flow secrete follistatin-like 1 protein which reduces transcytosis and inflammation},
url = {http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.025},
volume = {333},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background and aimsWhen endothelium is cultured in wells swirled on an orbital shaker, cells at the well centre experience putatively pro-atherogenic flow whereas those near the edge experience putatively atheroprotective flow. Transcellular transport is decreased equally in both regions, consistent with it being reduced by a mediator released from cells in one part of the well and mixed in the swirling medium. Similar effects have been reported for pro-inflammatory changes. Here we identify the mediator and the flow characteristics that stimulate its release.Methods and resultsMedium conditioned by cells swirled at the edge, but not by cells swirled at the centre or cultured under static conditions, significantly reduced transendothelial transport of a low density lipoprotein (LDL)-sized tracer and tumor necrosis factor α (TNF-α)-induced vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, activation of nuclear factor κB (NF-κB), and monocyte adhesion. An inhibitor of transcytosis similarly decreased tracer transport. Mass spectrometry identified follistatin-like 1 (FSTL1) as a candidate mediator. Cells from the swirled edge produced significantly more FSTL1 than cells from the swirled centre or from static wells. Exogenous FSTL1 reduced transendothelial transport of the LDL-sized tracer and of LDL itself, as well as TNF-α-induced VCAM-1 and ICAM-1 expression. Bone morphogenetic protein (4BMP4) increased transendothelial transport of the LDL-sized tracer and expression of VCAM-1 and ICAM-1; these effects were abolished by FSTL1.ConclusionsPutatively atheroprotective flow stimulates production of FSTL1 from cultured endothelial cells. FSTL1 reduces transcellular transport of LDL-sized particles and of LDL itself, and inhibits endothelial activation. If this also occurs in vivo, it may account for the atheroprotective nature of such flow.
AU  - Ghim,M
AU  - Pang,KT
AU  - Burnap,SA
AU  - Baig,F
AU  - Yin,X
AU  - Arshad,M
AU  - Mayr,M
AU  - Weinberg,PD
DO  - 10.1016/j.atherosclerosis.2021.08.025
EP  - 66
PY  - 2021///
SN  - 0021-9150
SP  - 56
TI  - Endothelial cells exposed to atheroprotective flow secrete follistatin-like 1 protein which reduces transcytosis and inflammation
T2  - Atherosclerosis
UR  - http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.025
UR  - https://www.sciencedirect.com/science/article/pii/S0021915021012867?via%3Dihub
UR  - http://hdl.handle.net/10044/1/91124
VL  - 333
ER  -
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