• The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure 

      Shahini, Negar; Bjørkelund, Elisabeth; Bendz, Christina; Massey, Richard J; Schjalm, Camilla; Halvorsen, Bente; Broch, Kaspar; Ueland, Thor; Gullestad, Lars; Nilsson, Per H.; Aukrust, Pål; Mollnes, Tom Eirik; Louwe, Maria Cornelia; Holt, Margrethe Flesvig; Michelsen, Annika E. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-24)
      Objective: Dysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with ...
    • The alternative complement pathway is dysregulated in patients with chronic heart failure 

      Shahini, Negar; Michelsen, Annika E.; Nilsson, Per H.; Ekholt, Karin; Gullestad, Lars; Broch, Kaspar; Dahl, Christen P.; Aukrust, Pål; Ueland, Thor; Mollnes, Tom Eirik; Yndestad, Arne; Louwe, Mieke C. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-14)
      The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured ...
    • The carnitine-butyrobetaine-TMAO pathway after cardiac transplant: Impact on cardiac allograft vasculopathy and acute rejection 

      Trøseid, Marius; Mayerhofer, Christiane Caroline; Broch, Kaspar; Arora, Satish; Svardal, Asbjørn M.; Hov, Johannes Espolin Roksund; Andreassen, Arne K.; Gude, Einar; Karason, Kristjan; Dellgren, Gøran; Berge, Rolf Kristian; Gullestad, Lars; Aukrust, Pål; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-19)
      <p><i>BACKGROUND - </i>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 ...
    • Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab 

      Woxholt, Sindre; Ueland, Thor; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar; Tøllefsen, Ingvild Maria; Ryan, Liv; Bendz, Bjørn; Hopp, Einar; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Halvorsen, Bente; Dahl, Tuva Børresdatter; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H.; Damås, Jan Kristian; Kleveland, Ola (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-17)
      Background - Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.<p> <p>Methods - STEMI patients were randomised to receive a single ...
    • Design of the GutHeart—targeting gut microbiota to treat heart failure—trial: a Phase II, randomized clinical trial 

      Mayerhofer, Christiane Caroline; Awoyemi, Ayodeji Olawale; Moscavitch, Samuel D.; Lappegård, Knut Tore; Hov, Johannes Espolin Roksund; Aukrust, Pål; Hovland, Anders; Lorenzo, Andrea; Halvorsen, Sigrun; Seljeflot, Ingebjørg; Gullestad, Lars; Trøseid, Marius; Broch, Kaspar (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-07)
      <p><i>Aims</i>: Heart failure (HF) is a multifactorial disease. Current treatments target only a fraction of the putative pathophysiological pathways. In patients with HF, reduced cardiac output and congestion cause increased gut wall permeability. It has been suggested that leakage of microbial products is detrimental to the heart, at least partly through activation of systemic inflammatory pathways, ...
    • Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension 

      Lekva, Tove; Gullestad, Lars; Broch, Kaspar; Aukrust, Pål; Andreassen, Arne K.; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-29)
      Activation of inflammatory processes has been identified as a major driver of pulmonary vascular remodeling that contributes to the development of precapillary pulmonary hypertension (PH). We hypothesized that circulating markers of leukocyte activation, reflecting monocytes/macrophages (sCD163, sCD14), T-cells (sCD25) and neutrophils (myeloperoxidase [MPO], neutrophil gelatinase-associated lipocalin ...
    • Increased secondary/primary bile acid ratio in chronic heart failure 

      Mayerhofer, Christiane Caroline; Ueland, Thor; Broch, Kaspar; Vincent, Royce P.; Cross, Gemma F.; Dahl, Christen Peder; Aukrust, Pål; Gullestad, Lars; Hov, Johannes Espolin Roksund; Trøseid, Marius (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-09-09)
      <p><i>Objective</i> Bile acids (BAs) are now recognized as signaling molecules and emerging evidence suggests that BAs affect cardiovascular function. The gut microbiota has recently been linked to the severity of heart failure (HF), and microbial metabolism has a major impact on BA homeostasis. We aimed to investigate the pattern of BAs, and particularly microbiota-transformed (secondary) BAs, in ...
    • Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial 

      Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar; Woxholt, Sindre; Yang, Kuan; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Quiles-Jiménez, Ana M T; Bjerkeli, Vigdis; Bendz, Christina; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Andersen, Geir Øystein; Wiseth, Rune; Halvorsen, Bente; Gullestad, Lars; Seljeflot, Ingebjørg; Aukrust, Pål; Osnes, Liv T. N.; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-30)
      Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear.<p> <p>Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI ...
    • 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 ...
    • Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure 

      Nendl, Andraz; Raju, Sajan; Broch, Kaspar; Mayerhofer, Christiane Caroline; Holm, Kristian; Halvorsen, Bente; Lappegård, Knut Tore; Moscavitch, Samuel; Hov, Johannes Espolin Roksund; Seljeflot, Ingebjørg; Trøseid, Marius; Awoyemi, Ayodeji Olawale (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-02)
      Background: The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this ...
    • 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 ...
    • 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 ...
    • 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 ...