PXD022068-1

PXD022068 is an original dataset announced via ProteomeXchange.

Title	Endothelial cells exposed to atheroprotective flow secrete follistatin-like protein 1 which reduces transcytosis and inflammation
Description	Objective - When endothelium is cultured in wells swirled on an orbital shaker, cells at the well centre experience putatively proatherogenic 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. Here we identify the mediator and the flow characteristics that stimulate its release. Approach and Results - Medium 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. Mass spectrometry identified follistatin-like 1 (FSTL1) as a candidate mediator. Cells from the swirled edge produced 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. An inhibitor of transcytosis similarly inhibited tracer transport. Exogenous FSTL1 and medium conditioned by cells swirled at the well edge also inhibited TNF-α-induced VCAM-1 and ICAM-1 expression, phosphorylation of IκBα, nuclear translocation of NF-κB, and monocyte adhesion. Conclusions - Putatively 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. The identification of a mediator linking flow to LDL transport suggests novel therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2021-08-23
AnnouncementXML	Submission_2021-08-23_00:39:57.096.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022068
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-19 03:54:12	ID requested
⏵ 1	2021-08-23 00:39:57	announced

Dataset with its publication pending

submitter keyword: Transverse wall shear stress

transWSS

multidirectional flow

vesicles

hemodynamics

permeability

endothelial activation

coronary artery disease

Manuel Mayr
contact affiliation	King's BHF Centre, King's College London, London, UK
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022068
     1. Label: PRIDE project
     2. Name: Endothelial cells exposed to atheroprotective flow secrete follistatin-like protein 1 which reduces transcytosis and inflammation