Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury

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dc.contributor.author Krebs, R.
dc.contributor.author Kankainen, M.
dc.contributor.author Holmström, E.
dc.contributor.author Dhaygude, K.
dc.contributor.author Lukac, J.
dc.contributor.author Ojala, T.
dc.contributor.author Mattila, P.
dc.contributor.author Nykänen, A.
dc.contributor.author Lemström, K.
dc.date.accessioned 2020-04-01T01:53:38Z
dc.date.available 2021-12-17T22:45:21Z
dc.date.issued 2019-04
dc.identifier.citation Krebs , R , Kankainen , M , Holmström , E , Dhaygude , K , Lukac , J , Ojala , T , Mattila , P , Nykänen , A & Lemström , K 2019 , ' Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury ' , Journal of Heart and Lung Transplantation , vol. 38 , no. 4, Supplement , pp. S75-S76 . https://doi.org/10.1016/j.healun.2019.01.171
dc.identifier.other PURE: 123381375
dc.identifier.other PURE UUID: edd0b179-1381-452c-8521-2cea8dfc870d
dc.identifier.other RIS: urn:452924701A8C6B313385A530C7CFD89F
dc.identifier.other WOS: 000461365100162
dc.identifier.other ORCID: /0000-0003-4499-6180/work/70950380
dc.identifier.other ORCID: /0000-0001-6920-4093/work/70951562
dc.identifier.other ORCID: /0000-0003-0418-8226/work/103594623
dc.identifier.uri http://hdl.handle.net/10138/313827
dc.description.abstract Purpose Numerous studies have shown that statin therapy initiated early after heart transplantation has beneficial effects on the development of cardiac allograft vasculopathy. Recently, we were able to show in a randomized clinical trial that simvastatin treatment of brain-dead donors conditions the heart transplant to withstand ischemia-reperfusion injury and to reduce the need for rejection treatments early after transplantation. In this study, we analyzed myocardial gene expression profiles in cardiac allografts after donor simvastatin treatment. Methods 84 heart transplant donors received 80 mg of simvastatin via nasogastric tube (n=42), or no treatment (n=42) in a prospective, double-blinded randomized controlled trial. Transmural Tru-Cut biopsies were taken from the apex of left ventricle of the donor heart immediately before reperfusion and 1 hour after reperfusion. 20 heart biopsies from donors without treatment and 20 heart biopsies from donors with simvastatin treatment will be analyzed with RNA sequencing. Results The preliminary analysis of RNA sequencing data from myocardial biopsies revealed altogether 137 significantly differentially expressed genes in all pairwise comparisons. The overall biological functions of these genes were related to gene ontology terms such as response to toxic substance, leukocyte migration, neutrophil mediated immunity, response to lipopolysaccharide, and response to oxidative stress. At the KEGG pathway level, our results indicated alterations in IL-17, TNF, MAPK and the AGE-RAGE signaling pathways. Conclusion We have shown in previous studies that donor simvastatin treatment induces protective effects against IRI in heart transplant recipients. In this study, we were able to detect significantly differentially expressed genes related to effects of simvastatin treatment. In order to single out genes that show beneficial effects of simvastatin treatment, further analysis will be conducted by exploring gene expression changes in specific biological functional categories, such as interleukin signaling and neutrophil degranulation. The complete analysis will be presented at the ISHLT 2019 congress. en
dc.format.extent 2
dc.language.iso eng
dc.relation.ispartof Journal of Heart and Lung Transplantation
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.title Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury en
dc.type Meeting Abstract
dc.contributor.organization Transplantation Laboratory
dc.contributor.organization Immunobiology Research Program
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Doctoral Programme in Biomedicine
dc.contributor.organization Clinicum
dc.contributor.organization Department of Pathology
dc.contributor.organization Doctoral Programme in Wildlife Biology
dc.contributor.organization Department of Pharmacology
dc.contributor.organization Staff Services
dc.contributor.organization Department of Surgery
dc.contributor.organization University Management
dc.contributor.organization Doctoral Programme in Clinical Research
dc.contributor.organization HUS Heart and Lung Center
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.healun.2019.01.171
dc.relation.issn 1053-2498
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion
dc.identifier.url http://www.sciencedirect.com/science/article/pii/S105324981930172X

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