PXD016228

PXD016228 is an original dataset announced via ProteomeXchange.

Title	Circulating endoglin induces hypertension via the upregulated expression of BMP4
Description	Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and often associated with increased levels of sEng. Although a pathogenic role for sEng involving hypertension has been reported in several animal models of preeclampsia, the exact molecular mechanisms implicated remain to be identified. To search for sEng-induced mediators, we have analyzed the protein secretome of human endothelial cells in the presence of sEng. We find that sEng induces the expression of BMP4 in endothelial cells, as evidenced by their proteomic signature, gene transcript levels and BMP4 promoter activity. A mouse model of preeclampsia with high sEng plasma levels (sEng+) showed increased levels of BMP4 transcripts in lungs and increased circulating BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appears 18 days after mating, precisely coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 are positively correlated in pregnant women with and without preeclampsia. Interestingly, sEng-induced arterial pressure elevation in sEng+ mice was abolished in the presence of the BMP4 inhibitor noggin, suggesting that BMP4 is a downstream mediator of sEng. These results provide a better understanding on the role of sEng in the pathobiology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.
HostingRepository	PRIDE
AnnounceDate	2020-04-27
AnnouncementXML	Submission_2020-04-26_23:00:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vivian de los Rios
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ4plex-116 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-11 06:48:37	ID requested
⏵ 1	2020-04-26 23:00:34	announced

Gallardo-Vara E, Gamella-Pozuelo L, Perez-Roque L, Bartha JL, Garcia-Palmero I, Casal JI, L, ó, pez-Novoa JM, Pericacho M, Bernabeu C, Potential Role of Circulating Endoglin in Hypertension via the Upregulated Expression of BMP4. Cells, 9(4):(2020) [pubmed]

submitter keyword: endoglin, endothelial cells, TGF-β, BMP4, hypertension, preeclampsia, HHT

Carmelo Bernabeu; J. Ignacio Casal
contact affiliation	Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid 28040, Spain.
contact email	vrios@cib.csic.es
lab head
Vivian de los Rios
contact affiliation	CIB.CSIC
contact email	vrios@cib.csic.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016228
     1. Label: PRIDE project
     2. Name: Circulating endoglin induces hypertension via the upregulated expression of BMP4