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dc.contributor.author | García-Redondo, Ana B | |
dc.contributor.author | Esteban, Vanesa | |
dc.contributor.author | Briones, Ana M | |
dc.contributor.author | Díaz Del Campo, Lucía S | |
dc.contributor.author | González-Amor, María | |
dc.contributor.author | Mendez-Barbero, Nerea | |
dc.contributor.author | Campanero, Miguel R | |
dc.contributor.author | Redondo, Juan Miguel | |
dc.contributor.author | Salaices, Mercedes | |
dc.date.accessioned | 2020-04-30T12:25:46Z | |
dc.date.available | 2020-04-30T12:25:46Z | |
dc.date.issued | 2018-07 | |
dc.identifier.citation | Pharmacol Res. 2018; 133:236-249 | es_ES |
dc.identifier.issn | 10436618 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9847 | |
dc.description.abstract | Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1+/+) and Rcan1-deficient (Rcan1-/-) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Vascular function and structure were analysed by myography. COX-2 and phospo-p65 expression were studied by western blotting and immunohistochemistry and TXA2 production by ELISA. We found that Rcan1 deficiency increases COX-2 and IL-6 expression and NF-κB activation in arteries and vascular smooth muscle cells (VSMC). Adenoviral-mediated re-expression of Rcan1.4 in Rcan1-/- VSMC normalized COX-2 expression. Phenylephrine-induced vasoconstrictor responses were greater in aorta from Rcan1-/- compared to Rcan1+/+ mice. This increased response were diminished by etoricoxib, furegrelate, SQ 29548, cyclosporine A and parthenolide, inhibitors of COX-2, TXA2 synthase, TP receptors, calcineurin and NF-κB, respectively. Endothelial removal and NOS inhibition increased phenylephrine responses only in Rcan1+/+ mice. TXA2 levels were greater in Rcan1-/- mice. In small mesenteric arteries, vascular function and structure were similar in both groups of mice; however, vessels from Rcan1-/- mice displayed an increase in vascular stiffness that was diminished by rofecoxib. In conclusion, our results suggest that Rcan1 might act as endogenous negative modulator of COX-2 expression and activity by inhibiting calcineurin and NF-kB pathways to maintain normal contractility and vascular stiffness in aorta and small mesenteric arteries, respectively. Our results uncover a new role for Rcan1 in vascular contractility and mechanical properties. | es_ES |
dc.description.sponsorship | This study was supported by Ministerio de Economia, Industria y Competitividad (MINECO) (SAF2012-36400 and SAF2016-80305-P), Institute de Salud Carlos III (ISCIII) (Red de Investigacion Cardiovascular, RD12/0042/0022 and RD12/0042/0024, CiberCV CB16/11/00286 and CB16/11/00264 and PI13/01488) Fondo Europeo de Desarrollo Regional (FEDER) a way to build Europe, Comunidad de Madrid (B2017/BMD-3676), COST BM1301 and Roche-IdiPaz. VE was supported by the Ramon y Cajal Program (RYC-2013-12880). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | COX-2 | es_ES |
dc.subject | Rcan1 | es_ES |
dc.subject | Vascular function and stiffness | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Aorta, Thoracic | es_ES |
dc.subject.mesh | Calcium-Binding Proteins | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Cyclooxygenase 2 | es_ES |
dc.subject.mesh | Intracellular Signaling Peptides and Proteins | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mesenteric Arteries | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Muscle Contraction | es_ES |
dc.subject.mesh | Muscle Proteins | es_ES |
dc.subject.mesh | Muscle, Smooth, Vascular | es_ES |
dc.subject.mesh | Myocytes, Smooth Muscle | es_ES |
dc.title | Regulator of calcineurin 1 modulates vascular contractility and stiffness through the upregulation of COX-2-derived prostanoids | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 29309904 | es_ES |
dc.format.volume | 133 | es_ES |
dc.format.page | 236-249 | es_ES |
dc.identifier.doi | 10.1016/j.phrs.2018.01.001 | es_ES |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Centro de Investigación Biomedica en Red - CIBER | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1096-1186 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.phrs.2018.01.001 | es_ES |
dc.identifier.journal | Pharmacological research | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamación | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2012-36400 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-80305-P | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0022 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD12/0042/0024 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CB16/11/00286 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CB16/11/00264 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI13/01488 | es_ES |
dc.rights.accessRights | open access | es_ES |