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PXD022068

PXD022068 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEndothelial cells exposed to atheroprotective flow secrete follistatin-like protein 1 which reduces transcytosis and inflammation
DescriptionObjective - 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.
HostingRepositoryPRIDE
AnnounceDate2021-08-23
AnnouncementXMLSubmission_2021-08-23_00:39:57.096.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD022068
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterXiaoke Yin
SpeciesList scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-19 03:54:12ID requested
12021-08-23 00:39:57announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Transverse wall shear stress
transWSS
multidirectional flow
vesicles
hemodynamics
permeability
endothelial activation
coronary artery disease
Contact List
Manuel Mayr
contact affiliationKing's BHF Centre, King's College London, London, UK
contact emailmanuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliationCardiovascular Division, King's College London
contact emailxiaoke.yin@kcl.ac.uk
dataset submitter
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