Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia

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dc.contributor.authorAutilio, Chiara
dc.contributor.authorEchaide Torreguitar, Mercedes
dc.contributor.authorCruz Rodríguez, Antonio
dc.contributor.authorHidalgo, A.
dc.contributor.authorDa Silva, E.
dc.contributor.authorDe Luca, Daniele
dc.contributor.authorSørli, Jorid B.
dc.contributor.authorPérez-Gil, Jesús
dc.date.accessioned2023-06-17T09:05:24Z
dc.date.available2023-06-17T09:05:24Z
dc.date.issued2020-01-12
dc.description.abstractTherapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant flms have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purifed porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperaturedependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of flms made of native surfactant. Lipid/protein mixtures designed as models to mimic diferent surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant flms exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more efective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Biológicas)
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN)
dc.description.sponsorshipComunidad de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/65603
dc.identifier.doi10.1038/s41598-020-79025-3
dc.identifier.issnESSN: 2045-2322
dc.identifier.officialurlhttps://www.nature.com/articles/s41598-020-79025-3
dc.identifier.urihttps://hdl.handle.net/20.500.14352/8143
dc.issue.number728
dc.journal.titleScientific Reports
dc.language.isoeng
dc.page.final14
dc.page.initial1
dc.publisherNature Research
dc.relation.projectID(RTI2018-094564-B-I00)
dc.relation.projectID(P2018/NMT-4389)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu577.112
dc.subject.cdu577.21
dc.subject.keywordLlung surfactant
dc.subject.keywordHypothermia
dc.subject.ucmBiología molecular (Biología)
dc.subject.ucmBioquímica (Biología)
dc.subject.unesco2415 Biología Molecular
dc.subject.unesco2302 Bioquímica
dc.titleMolecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
dc.typejournal article
dc.volume.number11
dspace.entity.typePublication
relation.isAuthorOfPublication23dc980e-fd18-48a1-aa1f-1c8537f97132
relation.isAuthorOfPublication9a800d46-4cd8-4a6d-97a1-4f2e9ce34f4e
relation.isAuthorOfPublicationcbc9b09a-1d4a-42e5-95c0-efb191f5d480
relation.isAuthorOfPublication.latestForDiscovery23dc980e-fd18-48a1-aa1f-1c8537f97132
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