2026-08-27T01:39:44Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1551822026-01-21T10:58:28Zcom_10366_154280com_10366_4512com_10366_3823col_10366_154281

Valbuena-Diez, Ana C Blanco, Francisco J. Oujo, Barbara Langa, Carmen González Núñez, María Llano Cuadra, María Elena Martín Pendás, Alberto Díaz, Mercedes Castrillo, Antonio López-Novoa, José M. Bernabeu, Carmelo 2024-02-01T16:32:32Z 2024-02-01T16:32:32Z 2012-11-27 Valbuena-Diez, A. C., Blanco, F. J., Oujo, B., Langa, C., Gonzalez-Nuñez, M., Llano, E., Pendas, A. M., Díaz, M., Castrillo, A., Lopez-Novoa, J. M., & Bernabeu, C. (2012). Oxysterol-induced soluble endoglin release and its involvement in hypertension. Circulation, 126(22), 2612–2624. https://doi.org/10.1161/CIRCULATIONAHA.112.101261 0009-7322 http://hdl.handle.net/10366/155182 10.1161/CIRCULATIONAHA.112.101261 23110859 1524-4539 [EN]Ischemia in the placenta is considered the base of the pathogenesis of preeclampsia, a pregnancy-specific syndrome in which soluble endoglin (sEng) is a prognostic marker and plays a pathogenic role. Here, we investigated the effects of hypoxia and the downstream pathways in the release of sEng. Under hypoxic conditions, the trophoblast-like cell line JAR showed an increase in sEng parallel to an elevated formation of reactive oxygen species. Because reactive oxygen species are related to the formation of oxysterols, we assessed the effect of 22-(R)-hydroxycholesterol, a natural ligand of the liver X receptor (LXR), and the LXR synthetic agonist T0901317. Treatment of JAR cells or human placental explants with 22-(R)-hydroxycholesterol or T0901317 resulted in a clear increase in sEng that was dependent on LXR. These LXR agonists induced an increased matrix metalloproteinase-14 expression and activity and a significant reduction of its endogenous inhibitor, tissue inhibitor of metalloproteinase-3. In addition, mice treated with LXR agonists underwent an increase in the plasma sEng levels, concomitant with an increase in arterial pressure. Moreover, transgenic mice overexpressing sEng displayed high blood pressure. Finally, administration of an endoglin peptide containing the consensus matrix metalloproteinase-14 cleavage site G-L prevented the oxysterol-dependent increase in arterial pressure and sEng levels in mice. These studies provide a clue to the involvement of the LXR pathway in sEng release and its pathogenic role in vascular disorders such as preeclampsia. Ministerio de Ciencia e Innovación; Genoma España (MEICA); Instituto Reina Sofía de Investigación Nefrológica (FRIAT); Junta de Castilla and León; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER); Red de Investigación Cooperativa en Enfermedades Renales (REDINREN) eng Lippincott Williams & Wilkins Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/embargoedAccess Cell hypoxia Hypertension Pre-eclampsia Pregnancy Peptides Antigens Anticholesteremic Agents Hydrocarbons Choriocarcinoma Hydroxycholesterols Orphan Nuclear Receptors Humans Cell Line Ischemia Blood Pressure Pre-Eclampsia Pregnancy Sulfonamides Human Umbilical Vein Endothelial Cells Intracellular Signaling Peptides and Proteins Tissue Inhibitor of Metalloproteinase-3 Placenta Diseases Animals Matrix Metalloproteinase 14 Uterine Neoplasms Mice hidrocarburos coriocarcinoma hidroxicolesteroles humanos ratones línea celular sulfonamidas presión sanguínea animales receptores nucleares huérfanos embarazo células endoteliales de la vena umbilical humana anticolesterolemiantes metaloproteinasa 14 de la matriz enfermedades placentarias isquemia neoplasias uterinas preeclampsia inhibidor tisular de la metaloproteinasa 3 antígenos péptidos y proteínas de señalización intracelular Oxysterol-induced soluble endoglin release and its involvement in hypertension info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion https://doi.org/10.1161/CIRCULATIONAHA.112.101261 SAF2010-61827 SAF2011-29244 SAF2010-15881 GR-100 Circulation 126 22 2612 2624