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Title

Potential Role of Circulating Endoglin in Hypertension via the Upregulated Expression of BMP4

AuthorsGallardo-Vara, Eunate ; Gamella-Pozuelo, Luis; Pérez-Roque, L.; Bartha, José L.; García-Palmero, Irene ; Casal, J. Ignacio ; López-Novoa, José M.; Pericacho, Miguel ; Bernabéu, Carmelo
KeywordsHypertension
Preeclampsia
HHT
Endoglin
Endothelial cells
TGF-β
BMP4
Issue Date16-Apr-2020
PublisherMultidisciplinary Digital Publishing Institute
CitationCells 9(4): 988 (2020)
AbstractEndoglin 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 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 of hypertension, we analyzed the protein secretome of human endothelial cells in the presence of sEng. We found 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 transcript levels of BMP4 in lungs, stomach, and duodenum, and increased circulating levels of BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appeared 18 days after mating, coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 were 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 physiopathology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.
Description© 2020 by the authors.
Publisher version (URL)https://doi.org/10.3390/cells9040988
URIhttp://hdl.handle.net/10261/209445
DOI10.3390/cells9040988
ISSN2073-4409
E-ISSN2073-4409
Appears in Collections:(CIB) Artículos
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