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dc.contributor.authorTrøseid, Mariusen_US
dc.contributor.authorMayerhofer, Christiane Carolineen_US
dc.contributor.authorBroch, Kasparen_US
dc.contributor.authorArora, Satishen_US
dc.contributor.authorSvardal, Asbjørn M.en_US
dc.contributor.authorHov, Johannes Espolin Roksunden_US
dc.contributor.authorAndreassen, Arne K.en_US
dc.contributor.authorGude, Einaren_US
dc.contributor.authorKarason, Kristjanen_US
dc.contributor.authorDellgren, Gøranen_US
dc.contributor.authorBerge, Rolf Kristianen_US
dc.contributor.authorGullestad, Larsen_US
dc.contributor.authorAukrust, Pålen_US
dc.contributor.authorUeland, Thoren_US
dc.PublishedTrøseid M, Mayerhofer CC, Broch K, Arora S, Svardal AM, Hov JR, Andreassen AK, Gude E, Karason K, Dellgren G, Berge RK, Gullestad L, Aukrust P, Ueland T. The carnitine-butyrobetaine-TMAO pathway after cardiac transplant: Impact on cardiac allograft vasculopathy and acute rejection. The Journal of Heart and Lung Transplantation. 2019;38(10):1097-1103eng
dc.descriptionUnder embargo until: 2020-06-19en_US
dc.description.abstractBACKGROUND: Alterations in the partly microbiota-dependent carnitine–γ-butyrobetaine (γBB)–trimethylamine N-oxide (TMAO) pathway have been linked to the progression of heart failure and atherosclerotic disease. We evaluated if circulating γBB, TMAO, and their common precursors carnitine and trimethyllysine (TML) were dysregulated after heart transplantation and associated with development of cardiac allograft vasculopathy (CAV) and acute rejection. METHODS: We measured these metabolites in plasma from heart transplant recipients with everolimus-based (n = 32) and standard cyclosporine-based immunosuppression (n = 30) at different time-points and accompanied by assessment of CAV by intravascular ultrasound. RESULTS: Baseline levels of carnitine, TMAO, and TML were elevated in heart transplant recipients compared with controls, and TML remained elevated throughout the observation period. The microbiota-dependent metabolite γBB increased steadily during 3 years of follow-up, with a similar decrease in its endogenous precursor TML. The increase in γBB and the change in TML were associated with a change in total atheroma volume from baseline to 3 years. Increases in γBB and carnitine levels from baseline to 1 year were associated with an increased frequency of acute rejection within the first year after heart transplant. CONCLUSIONS: Our study reveals alterations of the carnitine-γBB-TMAO pathway after heart transplant, with increasing levels of γBB being associated with acute rejection and increase in total atheroma volume during 3 years of follow-up. Future studies should clarify whether interactions between dietary factors, immunosuppressive drugs, and the gut microbiota could influence acute rejection and CAV development to delineate mechanisms and potential novel treatment targets.en_US
dc.rightsAttribution CC BY-NC-NDeng
dc.titleThe carnitine-butyrobetaine-TMAO pathway after cardiac transplant: Impact on cardiac allograft vasculopathy and acute rejectionen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 Elsevier
dc.source.journalThe Journal of Heart and Lung Transplantation

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