PXD036260-2

PXD036260 is an original dataset announced via ProteomeXchange.

Title	Physiological shear stress markedly alters the proteomic response to hypoxia in human pulmonary microvascular endothelial cells
Description	Physiological shear stress, produced by blood flow, homeostatically regulates the phenotype of pulmonary endothelial cells exerting anti-inflammatory and anti-thrombotic actions and maintaining normal barrier function. In the pulmonary circulation hypoxia, due to high altitude or diseases such as COPD, causes vasoconstriction, increased vascular resistance and pulmonary hypertension. Hypoxia-induced changes in endothelial function play a central role in the development of this pulmonary hypertension. However, the direct interactive effects of hypoxia and shear stress on the pulmonary endothelial phenotype have not been extensively studied. We cultured human pulmonary microvascular endothelial cells (HPMEC) in normoxia or hypoxia while subjected to physiological shear stress or in static conditions. Unbiased proteomics was used to identify hypoxia-induced changes in protein expression. Using publicly available single cell RNA-seq datasets, differences in gene expression between the alveolar endothelial cells from COPD and healthy lungs were identified. 60 proteins were identified in HPMEC lysates whose expression changed in response to hypoxia in sheared but not in static conditions. mRNA for five of these (ERG, MCRIP1, EIF4A2, HSP90AA1 and DNAJA1) showed similar changes in the endothelial cells of COPD compared to healthy lungs. These data show that the proteomic responses of the pulmonary microvascular endothelium to hypoxia are significantly altered by shear stress and suggest that these differences are important in the development of hypoxic pulmonary vascular disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:10:34.677.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036260
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eugene Dillon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 13:04:24	ID requested
1	2023-02-17 02:28:48	announced
⏵ 2	2023-11-14 08:10:35	announced	2023-11-14: Updated project metadata.

10.6019/PXD036260;

Kostyunina DS, Rowan SC, Pakhomov NV, Dillon E, Rochfort KD, Cummins PM, O'Rourke MJ, McLoughlin P, Shear Stress Markedly Alters the Proteomic Response to Hypoxia in Human Pulmonary Endothelial Cells. Am J Respir Cell Mol Biol, 68(5):551-565(2023) [pubmed]

submitter keyword: shear stress, COPD,Human pulmonary microvascular endothelial cells, hypoxia

Paul McLoughlin
contact affiliation	School of Medicine, University College Dublin, Dublin, Ireland
contact email	paul.mcloughlin@ucd.ie
lab head
Eugene Dillon
contact affiliation	UCD
contact email	eugene.dillon@ucd.ie
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/02/PXD036260

PRIDE project URI

• PRIDE
  1. PXD036260
     1. Label: PRIDE project
     2. Name: Physiological shear stress markedly alters the proteomic response to hypoxia in human pulmonary microvascular endothelial cells