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dc.contributor.authorDiekmann, Franziska
dc.contributor.authorChouvarine, Philippe
dc.contributor.authorSallmon, Hannes
dc.contributor.authorMeyer-Kobbe, Louisa
dc.contributor.authorKieslich, Moritz
dc.contributor.authorPlouffe, Brian D
dc.contributor.authorMurthy, Shashi K
dc.contributor.authorLichtinghagen, Ralf
dc.contributor.authorLegchenko, Ekaterina
dc.contributor.authorHansmann, Georg
dc.date.accessioned2021-10-26T23:30:33Z
dc.date.available2021-10-26T23:30:33Z
dc.date.issued2021-08-10
dc.identifier.issn1661-6596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329920
dc.description.abstractPulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls (p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.
dc.format.mediumElectronic
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectPrognosis
dc.subjectSensitivity and Specificity
dc.subjectCase-Control Studies
dc.subjectSolubility
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectGermany
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectBiomarkers
dc.subjectReceptor for Advanced Glycation End Products
dc.subjectPulmonary Arterial Hypertension
dc.titleSoluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension.
dc.typeArticle
prism.issueIdentifier16
prism.publicationDate2021
prism.publicationNameInt J Mol Sci
prism.volume22
dc.identifier.doi10.17863/CAM.77363
dcterms.dateAccepted2021-07-29
rioxxterms.versionofrecord10.3390/ijms22168591
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-08-10
dc.contributor.orcidDiekmann, Franziska [0000-0003-3923-9492]
dc.contributor.orcidPlouffe, Brian D [0000-0002-1576-5714]
dc.contributor.orcidLegchenko, Ekaterina [0000-0001-7949-2973]
dc.contributor.orcidHansmann, Georg [0000-0003-0709-3935]
dc.identifier.eissn1422-0067
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-08-10


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International