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dc.contributor.authorRoche-Molina, Marta 
dc.contributor.authorHardwick, Bryn
dc.contributor.authorSanchez-Ramos, Cristina
dc.contributor.authorSanz-Rosa, David 
dc.contributor.authorGewert, Dirk
dc.contributor.authorCruz, Francisco Miguel 
dc.contributor.authorGonzalez-Guerra, Andres
dc.contributor.authorAndres, Vicente 
dc.contributor.authorPalma, Joaquin A
dc.contributor.authorIbanez, Borja 
dc.contributor.authorMckenzie, Grahame
dc.contributor.authorBernal, Juan Antonio
dc.identifier.citationSci Rep. 2020; 10(1):11636es_ES
dc.description.abstractN-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.es_ES
dc.description.sponsorshipThe CNIC is supported by the Ministry of Science and Innovation and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This study was supported by the Ministry of Science and Innovation grant BFU2016-75144-Res_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.titleThe pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis.es_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderFundación ProCNIC
dc.identifier.journalScientific reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Cardiomiopatías de origen genéticoes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES

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Atribución 4.0 Internacional
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