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Identification of human circulating factors following remote ischemic conditioning (RIC)

dc.contributor.authorMollet, Inês G.
dc.contributor.authorViana-Soares, Ricardo
dc.contributor.authorCardoso-Pires, Catarina
dc.contributor.authorSoares, Nuno L.
dc.contributor.authorMarto, João Pedro
dc.contributor.authorMendonça, Marcelo
dc.contributor.authorQueiroga, Cláudia S.F.
dc.contributor.authorCarvalho, Ana S.
dc.contributor.authorSequeira, Catarina O.
dc.contributor.authorTeixeira-Santos, Luísa
dc.contributor.authorFernandes, Tatiana P.
dc.contributor.authorAloria, Kerman
dc.contributor.authorPereira, Sofia A.
dc.contributor.authorSA, Pereira
dc.contributor.authorMatthiesen, Rune
dc.contributor.authorMatthiesen, Rune
dc.contributor.authorViana-Baptista, Miguel
dc.contributor.authorVieira, Helena L.A.
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.pblElsevier
dc.date.accessioned2024-10-03T22:25:58Z
dc.date.available2024-10-03T22:25:58Z
dc.date.issued2024-11-01
dc.descriptionFunding Information: The funding agency that supported the work \u201CFunda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia\u201D (FCT) with four projects: Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019), iNOVA4Health - Programme in Translational Medicine (UID/Multi/04462/2013), LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy and PTDC/MEC-NEU/28750/2017 and the PhD scholarship for NLS (PD/BD/127819/2016). Publisher Copyright: © 2024 The Authors
dc.description.abstractRemote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed. RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent16
dc.format.extent7224106
dc.identifier.doi10.1016/j.freeradbiomed.2024.08.017
dc.identifier.issn0891-5849
dc.identifier.otherPURE: 100587085
dc.identifier.otherPURE UUID: 7bb934a5-d39f-46c4-ae11-299540048947
dc.identifier.otherScopus: 85201461825
dc.identifier.otherPubMed: 39151835
dc.identifier.otherORCID: /0000-0002-1422-1336/work/168877008
dc.identifier.otherORCID: /0000-0001-9415-3742/work/168877380
dc.identifier.otherORCID: /0000-0002-8456-9995/work/168877613
dc.identifier.urihttp://hdl.handle.net/10362/172955
dc.identifier.urlhttps://www.scopus.com/pages/publications/85201461825
dc.language.isoeng
dc.peerreviewedyes
dc.subjectBiomarkers
dc.subjectNeuroinflammation
dc.subjectOxidative stress
dc.subjectProteomics
dc.subjectRemote ischemic (pre)conditioning
dc.subjectStroke
dc.subjectBiochemistry
dc.subjectPhysiology (medical)
dc.subjectSDG 3 - Good Health and Well-being
dc.titleIdentification of human circulating factors following remote ischemic conditioning (RIC)en
dc.title.subtitlePotential impact on strokeen
dc.typejournal article
degois.publication.firstPage23
degois.publication.lastPage38
degois.publication.titleFree Radical Biology And Medicine
degois.publication.volume224
dspace.entity.typePublication
person.familyNamede Azeredo Pereira
person.familyNameMatthiesen
person.givenNameSofia
person.givenNameRune
person.identifier562223
person.identifier1319342
person.identifier.ciencia-id6B13-7601-73A2
person.identifier.ciencia-idBB1A-A606-EE77
person.identifier.orcid0000-0002-8456-9995
person.identifier.orcid0000-0002-6353-2616
person.identifier.ridM-2976-2019
person.identifier.scopus-author-id35190948700
person.identifier.scopus-author-id9741897800
rcaap.rightsopenAccess
relation.isAuthorOfPublicationf4809377-832b-40b5-92ca-0bb1c6fe14f3
relation.isAuthorOfPublication67181d3c-b83e-4151-9a74-0ea14aeb7f05
relation.isAuthorOfPublication.latestForDiscovery67181d3c-b83e-4151-9a74-0ea14aeb7f05

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