• Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction 

      Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte; Yndestad, Arne; Broch, Kaspar; Holte, Espen; Ryan, Liv; Amundsen, Brage H.; Bendz, Bjørn; Aakhus, Svend; Espevik, Terje; Halvorsen, Bente; Mollnes, Tom Eirik; Wiseth, Rune; Gullestad, Lars; Aukrust, Pål; Damås, Jan Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-29)
      <p><i>Aim</i>: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).</p> <p><i>Methods</i>: 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive ...
    • Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages 

      Lunde, Ngoc Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre; Kong, Xiang Yi; Michelsen, Annika; Otterdal, Kari; Yndestad, Arne; Broch, Kaspar; Gullestad, Lars; Nyman, Tuula Anneli; Bendz, Bjørn; Eritsland, Jan; Hoffmann, Pavel; Skagen, Karolina Ryeng; Gonçalves, Isabel; Nilsson, Jan; Grenegård, Magnus; Poreba, Marcin; Drag, Marcin; Seljeflot, Ingebjørg; Sporsheim, Bjørnar; Espevik, Terje; Skjelland, Mona; Johansen, Harald Thidemann; Solberg, Rigmor; Aukrust, Pål; Björbacka, Harry; Andersen, Geir Øystein; Halvorsen, Bente (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-14)
      <i>Background and aims</i> - We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events.<p><p> <i>Methods</i> - Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent ...
    • Microvascular function and inflammatory activation in Takotsubo cardiomyopathy 

      Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Ueland, Thor; Gullestad, Lars; Aukrust, Pål; Stavem, Knut (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-03)
      Aims - The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS-induced pathology.<p> <p>Methods and results - The study included 20 females [median age 65 years; interquarile range (IQR) = 58–70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, ...
    • Novel Insights Into the Effects of Interleukin 6 Antagonism in Non-ST-Segment-Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform 

      George, Marc J; Kleveland, Ola; Garcia-Hernandez, Jorge; Palmen, Jutta; Lovering, Ruth; Wiseth, Rune; Aukrust, Pål; Engmann, Jorgen; Damås, Jan Kristian; Hingorani, Aroon D; Gullestad, Lars; Casas, Juan P; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-09)
      <p>Background: Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab non-ST-segment-elevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both C-reactive protein and troponin T were reduced in the active treatment arm. In ...
    • Pro-gastrin-releasing peptide and outcome in patients with heart failure and anaemia: results from the RED-HF study 

      Ueland, Thor; Gullestad, Lars; Kou, Lei; Aukrust, Pål; Anand, Inder S.; Nordlund, Marianne Sparby; McMurray, John J.; van Veldhuisen, Dirk J.; Warren, David; Bolstad, Nils (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-25)
      <p><i>Aims</i>: Neuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin‐releasing peptide (GRP), derived from the precursor proGRP1‐125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction.</p> <p><i>Methods and ...
    • Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction 

      Broch, Kaspar; Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend; Bjørkelund, Elisabeth; Bendz, Christina; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-12)
      <p><i>Background - </i>Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. <p><i>Objectives - </i>This study sought ...
    • Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI) 

      Anstensrud, Anne Kristine; Voxholt, Sindre; Sharma, Kapil; Broch, Kaspar; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-15)
      <i>Introduction</i>: Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through ...
    • Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial 

      Awoyemi, Ayodeji Olawale; Mayerhofer, Cristiane; Felix, Alex S.; Hov, Johannes Espolin Roksund; Moscavitch, Samuel D.; Lappegård, Knut Tore; Hovland, Anders; Halvorsen, Sigrun; Halvorsen, Bente; Gregersen, Ida; Svardal, Asbjørn M.; Berge, Rolf Kristian; Hansen, Simen Hyll; Götz, Alexandra; Holm, Kristian; Aukrust, Pål; Åkra, Sissel; Seljeflot, Ingebjørg; Solheim, Svein; Lorenzo, Andrea; Gullestad, Lars; Trøseid, Marius; Broch, Kaspar (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-28)
      Background - The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF).<p> <p>Methods - In a multicentre, prospective randomized open label, blinded ...
    • Rosuvastatin alters the genetic composition of the human gut microbiome 

      Kummen, Martin; Solberg, Ole Geir; Larsen, Christopher Storm; Holm, Kristian; Ragnarsson, Asgrimur; Trøseid, Marius; Vestad, Beate; Skårdal, Rita; Yndestad, Arne; Ueland, Thor; Svardal, Asbjørn M.; Berge, Rolf Kristian; Seljeflot, Ingebjørg; Gullestad, Lars; Karlsen, Tom Hemming; Aaberge, Lars; Aukrust, Pål; Hov, Johannes Espolin Roksund (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-25)
      The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled ...
    • Secreted frizzled related protein 3 in chronic heart failure: Analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA) 

      Askevold, Erik Tandberg; Gullestad, Lars; Nymo, Ståle Haugset; Kjekshus, John; Yndestad, Arne; Latini, Roberto; Cleland, John G.F.; McMurray, John J.V.; Aukrust, Pål; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-08-19)
      Background We have previously demonstrated an association between increased sFRP3 expression and adverse outcome in a population of HF irrespective of cause and left ventricular ejection fraction. In this study we evaluated the prognostic value of sFRP3 in older patients with chronic systolic HF of ischemic origin. <p>Methods We evaluated sFRP3, by tertiles, as a risk factor for the primary ...
    • Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction 

      Ueland, Thor; Kleveland, Ola; Michelsen, Annika; Wiseth, Rune; Damås, Jan Kristian; Aukrust, Pål; Gullestad, Lars; Halvorsen, Bente; Yndestad, Arne (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-18)
      <p><i>Objective</i>: It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.</p> <p><i>Approach</i>: We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels ...
    • T cell and monocyte/macrophage activation markers associate with adverse outcome, but give limited prognostic value in anemic patients with heart failure: results from RED-HF 

      Abraityte, Aurelija; Aukrust, Pål; Kou, Lei; Anand, Inder S.; Young, James; Mcmurray, John J.V.; van Veldhuisen, Dirk J.; Gullestad, Lars; Ueland, Thor (Journal article; Tidsskriftartikkel, 2018-07-26)
      <i>Background</i>: Activated leukocytes may contribute to the development and progression of heart failure (HF). We investigated the predictive value of circulating levels of stable and readily detectable markers reflecting both monocyte/macrophage and T-cell activity, on clinical outcomes in HF patients with reduced ejection fraction (HFrEF).<p> <p><i>Methods</i>: The association between ...
    • Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction 

      Helseth, Ragnhild; Kleveland, Ola; Ueland, Thor; Wiseth, Rune; Damås, Jan Kristian; Broch, Kaspar; Michelsen, Annika Elisabet; Bendz, Bjørn; Gullestad, Lars; Aukrust, Pål; Seljeflot, Ingebjørg (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-10)
      Objective: Beyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties.<p> <p>Methods - In a placebo-controlled ...
    • Wnt5a is associated with right ventricular dysfunction and adverse outcome in dilated cardiomyopathy 

      Abraityte, Aurelija; Lunde, Ida Gjervold; Askevold, Erik Tandberg; Michelsen, Annika E.; Christensen, Geir Arve; Aukrust, Pål; Yndestad, Arne; Fiane, Arnt; Andreassen, Arne; Aakhus, Svend; Dahl, Christen Peder; Gullestad, Lars; Broch, Kaspar; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-14)
      The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFAT luciferase activity in neonatal mouse cardiomyocytes. Elevated circulating Wnt5a (n = 102) was associated ...
    • YKL-40 (Chitinase-3-Like Protein 1) Serum Levels in Aortic Stenosis 

      Arain, Fizza Kanwal; Abraityte, Judita Aurelija; Bogdanova, Mariia; Solberg, Ole Geir; Michelsen, Annika; Lekva, Tove; Aakhus, Svend; Holm, Sverre; Halvorsen, Bente; Finsen, Alexandra; Vinge, Leif Erik; Nymo, Ståle Haugset; Espeland, Torvald; Ranheim, Trine; Aukrust, Pål; Vaage, Ingvar Jarle; Auensen, Andreas; Gullestad, Lars; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-23)
      <p><i>Background:</i> Identification of novel biomarkers could provide prognostic information and improve risk stratification in patients with aortic stenosis (AS). YKL-40 (chitinase-3-like protein 1), a protein involved in atherogenesis, is upregulated in human calcific aortic valves. We hypothesized that circulating YKL-40 would be elevated and associated with the degree of AS severity and outcome ...