Immune regulation in atherosclerosis and other cardiometabolic diseases

Cardiovascular disease and related metabolic disorders such as diabetes, obesity and fatty liver disease are major causes of morbidity and mortality worldwide. They have many common features, such as dyslipidemia and inflammation. In our research group we focus on immune-mediated mechanisms in these conditions.

The last years we have also studied these mechanisms in Covid-19, and the association between Covid-19 and risk of cardiovascular disease.

By exploring these processes through translational research, connecting basic science and the clinic, we wish to build a foundation for the development of new diagnostic and treatment targets for cardiometabolic disease.

Our research group works in the cross-section between molecular biology and biochemistry, and cardiovascular, cerebrovascular, and endocrine medicine. Our ambitious goal is to delineate novel therapeutic targets and biomarkers.

The group uses different research approaches, ranging from analyses of blood and tissue samples from patients to studies in genetically modified mice and cell culture systems, using advanced cellular and molecular biology.

The group consists of people with different educational background and includes medical doctors, nutritionists, biochemists, and engineers. Such multidisciplinary competence is a great strength of our research group.

The research group is a part of the Research Institute of internal medicine at Rikshospitalet. Tuva Børresdatter Dahl is acting group leader while Bente Halvorsen is on a sabbatical scholar in the USA during 2022/23.

Projects

The group runs a large span of interconnected translational projects to study the immunological and molecular mechanisms in obesity, metabolic disorders, cardiovascular disease and Covid-19; which share many common features.

We study the following processes in these conditions to improve our understanding of the underlying ethology and to identify new biomarkers and treatment targets.

• Regulation and role of innate and adaptive immune response

• DNA repair mechanisms and genome stability 

• Pain sensitivity and vascular inflammation

• Fish oil supplements and cardiometabolism

Project group leaders are Tuva Børresdatter Dahl, Ida Gregersen and Xiang Yi Kong.

Cooperation

Our research group has both national and international partners.

National

• Lars Gullestad, UiO/OUH

• Mona Skjelland, UiO/OUH

• Anne Hege Åmodt, UiO/OUH 

• Karolina Ryeng Skagen,OUH

• Kjetil Taskén, UiO/OUH

• Kåre Birkeland/ UiO/OUH

• Kirsten B. Holven, UiO/OUH

• Arild Rustan, UiO

• Leiv Arne Rosseland, UiO/OUH

• Terje Espevik, NTNU

• Christopher Sivert Nielsen, NIPH

• Rigmor Solberg, UiO

• Ingrun Alseth, OUH

• Anne Ma Dyrhol-Riise,, UiO/OUH

• Jan Cato Holter, OUH

• Andreas Barratt-Due, OUH

• Geir Øystein Andersen, OUH

• Kaspar Broch, OUH

• Magnar Bjørås, NTNU/UiO

• Tom Eirik Mollnes, UiO/OUS/Nordland Hospital, Bodø/NTNU

• Bjørnar Hassel UiO/OUH

• Pål Andre Holme UiO/OUH

• Ivar Sjaastad, UiO/OUH

• Ludvig Munthe, UiO

• Azhar Abbas, Sykehuset Østfold Kalnes

International

• Erik Biessen, Maastricht University, the Netherlands

• Harry Björkbacka, University of Lund, Sweden

• Jan Boren, University of Gothenburg, Sweden

• Eicke Latz, University of Bonn, Germany

• Patrick Rensen, Leiden University, the Netherlands

• Peter  Libby, Harvard Medical School, Boston, US

• Thomas Ulas, University of Bonn, Germany 

•  Martin Bennett, University of Cambridge, UK

• Thorgeir Thorgeirsson, DECODE, Iceland

• Rafael Maldonado, University Pompeu Fabra, Spain

• Joyce van Meurs, Erasmus MC, the Netherlands

• Laura Harsan, University of Strasbourg, France

• Isabel Goncalves, University of Lund, Sweden

• Åsa Tivesten, University of Gothenburg, Sweden

Selected publications

• Halvorsen, B., P. Aukrust, T.B. Dahl, I. Gregersen, Increased cardiovascular mortality during the COVID-19 pandemic: do not neglect causality. Eur Heart J Open, 2023. 3(6): oead119.
• Murphy, S.L., B. Halvorsen, J.C. Holter, C. Huse, A. Tveita, M. Trøseid, H. Hoel, A.B. Kildal, A.R. Holten, T.V. Lerum, O.H. Skjønsberg, A.E. Michelsen, T.M. Aaløkken, K. Tonby, A. Lind, S. Dudman, B.K. Granerud, L. Heggelund, S. Bøe, A.M. Dyrholt-Riise, P. Aukrust, A. Barratt-Due, T. Ueland, T.B. Dahl, Circulating markers of extracellular matrix remodelling in severe COVID-19 patients. J Intern Med, 2023. 294(6): 784-797.
• Quiles-Jiménez, A., M.M.L. Sousa, C. Huse, A.M. Dyrhol-Riise, J.C. Holter, E.E. Christensen, K. Tonby, A.R. Holten, P. Aukrust, M. Bjørås, T.B. Dahl, B. Halvorsen, Severely ill COVID-19 patients have altered circulating levels of proteins controlling the epitranscriptome. J Infect, 2023. 86(6): 593-595.
• Ueland, T., L.A.O. Äikäs, T.B. Dahl, I. Gregersen, M.B. Olsen, A. Michelsen, Y. Schanke, M. Holopainen, H. Ruhanen, S. Singh, A.A. Tveita, A.K. Finbråten, L. Heggelund, M. Trøseid, A.M. Dyrhol-Riise, T.A. Nyman, K.B. Holven, K. Öörni, P. Aukrust, B. Halvorsen, Low-density lipoprotein particles carrying proinflammatory proteins with altered aggregation pattern detected in COVID-19 patients 3 months after hospitalization. J Infect, 2023.
• Bjørnebekk, A., M. Scarth, S.P. Neupane, L.T. Westlye, I.R. Hullstein, P.M. Thorsby, B. Halvorsen, Use of high-dose androgens is associated with reduced brain derived neurotrophic factor in male weightlifters. Neuroendocrinology, 2022.
• Huse, C., A.K. Anstensrud, A.E. Michelsen, T. Ueland, K. Broch, S. Woxholt, K. Yang, K. Sharma, I.M. Tøllefsen, B. Bendz, B.H. Amundsen, J.K. Damås, E.S. Berg, E. Bjørkelund, A. Quiles-Jiménez, V. Bjerkeli, C. Bendz, O. Kleveland, K.H. Stensaeth, A. Opdahl, N.E. Kløw, G. Andersen, R. Wiseth, B. Halvorsen, L. Gullestad, I. Seljeflot, P. Aukrust, L. Osnes, T.B. Dahl, Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial. EBioMedicine, 2022. 80: 104013.
• Holm, S., H. Kared, A.E. Michelsen, X.Y. Kong, T.B. Dahl, N.H. Schultz, T.A. Nyman, C. Fladeby, I. Seljeflot, T. Ueland, M. Stensland, S. Mjaaland, G.L. Goll, L.S. Nissen-Meyer, P. Aukrust, K. Skagen, I. Gregersen, M. Skjelland, P.A. Holme, L.A. Munthe, B. Halvorsen, Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia. Eur Heart J, 2021. 42(39): 4064-4072.
• Lauritzen, K.H., M.B. Olsen, M.S. Ahmed, K. Yang, J.E. Rinholm, L.H. Bergersen, Q.Y. Esbensen, L.J. Sverkeli, M. Ziegler, H. Attramadal, B. Halvorsen, P. Aukrust, A. Yndestad, Instability in NAD(+) metabolism leads to impaired cardiac mitochondrial function and communication. Elife, 2021. 10.
• Niyonzima, N., J. Rahman, N. Kunz, E.E. West, T. Freiwald, J.V. Desai, N.S. Merle, A. Gidon, B. Sporsheim, M.S. Lionakis, K. Evensen, B. Lindberg, K. Skagen, M. Skjelland, P. Singh, M. Haug, M.M. Ruseva, M. Kolev, J. Bibby, O. Marshall, B. O'Brien, N. Deeks, B. Afzali, R.J. Clark, T.M. Woodruff, M. Pryor, Z.H. Yang, A.T. Remaley, T.E. Mollnes, S.M. Hewitt, B. Yan, M. Kazemian, M.G. Kiss, C.J. Binder, B. Halvorsen, T. Espevik, C. Kemper, Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation. Sci Immunol, 2021. 6(66): eabf2489. 
• Quiles-Jiménez, A., I. Gregersen, F.M. Segers, T. Skarpengland, P. Kroustallaki, K. Yang, X.Y. Kong, K.H. Lauritzen, M.B. Olsen, T.R. Karlsen, T.A. Nyman, E.L. Sagen, V. Bjerkeli, R. Suganthan, S. Nygård, K. Scheffler, J. Prins, E. Van der Veer, J.D. Øgaard, Y. Fløisand, H.F. Jørgensen, K.B. Holven, E.A. Biessen, H. Nilsen, T.B. Dahl, S. Holm, M.R. Bennett, P. Aukrust, M. Bjørås, B. Halvorsen, DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development. Atherosclerosis, 2021. 324: 123-132.
• Gregersen, I., A.E. Michelsen, N.N. Lunde, A. Åkerblom, T.G. Lakic, M. Skjelland, K. Ryeng Skagen, R.C. Becker, J. Lindbäck, A. Himmelmann, R. Solberg, H.T. Johansen, S.K. James, A. Siegbahn, R.F. Storey, F. Kontny, P. Aukrust, T. Ueland, L. Wallentin, B. Halvorsen, Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial. J Am Heart Assoc, 2020. 9(17): e016360.
• Louwe, M.C., M.B. Olsen, O.J. Kaasbøll, K. Yang, L.E. Fosshaug, K. Alfsnes, J.D.S. Øgaard, A. Rashidi, V.M. Skulberg, M. Yang, D. de Miranda Fonseca, A. Sharma, J.M. Aronsen, E. Schrumpf, M.S. Ahmed, C.P. Dahl, T.A. Nyman, T. Ueland, E. Melum, B.E. Halvorsen, M. Bjørås, H. Attramadal, I. Sjaastad, P. Aukrust, A. Yndestad, Absence of NLRP3 Inflammasome in Hematopoietic Cells Reduces Adverse Remodeling After Experimental Myocardial Infarction. JACC Basic Transl Sci, 2020. 5(12): 1210-1224.
• Niyonzima, N., S.S. Bakke, I. Gregersen, S. Holm, Ø. Sandanger, H.L. Orrem, B. Sporsheim, L. Ryan, X.Y. Kong, T.B. Dahl, M. Skjelland, K.K. Sørensen, A.M. Rokstad, A. Yndestad, E. Latz, L. Gullestad, G. Andersen, J.K. Damås, P. Aukrust, T.E. Mollnes, B. Halvorsen, T. Espevik, Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis. EBioMedicine, 2020. 60: 102985.