Tønnessen group: Myocardial remodeling and reverse remodeling in pressure overload

Our group is conducting experimental/translational research studying cardiac pathophysiology related to aortic stenosis and pressure overload.

About the group

Aortic stenosis is the most common valvular lesion in the western world. In patients with aortic stenosis, excessive myocardial remodeling (hypertrophy, fibrosis and expression of fetal genes) leads to increased operative risk during aortic valve replacement (AVR). There is currently no effective treatment for postoperative low-output syndrome due to diastolic dysfunction, making this a major challenge in cardiac surgery. Incomplete reverse remodeling after AVR for aortic stenosis is associated with persisting symptoms and increased mortality. Hence, studies addressing myocardial remodeling and reverse myocardial remodeling are warranted.

We have established a mouse model of reversible left ventricular pressure overload mimicking AVR for aortic stenosis and found novel extracellular matrix (ECM) changes during reverse remodeling. To extend these findings we have planned further studies including a “loss of function” approach.

We will use a genetically modified mice to examine the importance of specific extracellular matrix constituents in remodeling and reverse remodeling after relief of pressure overload.

Specifically we want to reveal the importance of the SMAD signalling system in pressure overload. We have found that inhibition of SMAD2 by a small peptide inhibitor (SM16) improves cardiac function, possibly due to effects on SERCA2 and intracellular calcium handling.

Moreover, we have recently focused on the role of proteoglycans (especially lumican and fibromodulin) in myocardial remodeling and function, and their role in whether a pressure overloaded or ischemic heart is transformed from compensated to decompensated heart failure.

Professor Theis Tønnessen is group leader of this associated group.

Group Leader

Theis Tønnessen

Group Leader & Professor & Senior Consultant

Latest publications

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Ruud M, Frisk M, Melleby AO, Norseng PA, Mohamed BA, Li J, Aronsen JM, Setterberg IE, Jakubiczka J, van Hout I, Coffey S, Shen X, Nygård S, Lunde IG, Tønnessen T, Jones PP, Sjaastad I, Gullestad L, Toischer K, Dahl CP, Christensen G, Louch WE (2024)
Regulation of cardiomyocyte t-tubule structure by preload and afterload: Roles in cardiac compensation and decompensation
J Physiol
PubMed 38686538 DOI 10.1113/JP284566
Vistnes M, Erusappan PM, Sasi A, Nordén ES, Bergo KK, Romaine A, Lunde IG, Zhang L, Olsen MB, Øgaard J, Carlson CR, Wang CH, Riise J, Dahl CP, Fiane AE, Hauge-Iversen IM, Espe E, Melleby AO, Tønnessen T, Aronsen JM, Sjaastad I, Christensen G (2023)
Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction
Cardiovasc Res, 119 (10), 1915-1927
PubMed 37216909 DOI 10.1093/cvr/cvad078
Strand ME, Vanhaverbeke M, Henkens MTHM, Sikking MA, Rypdal KB, Braathen B, Almaas VM, Tønnessen T, Christensen G, Heymans S, Lunde IG (2023)
Inflammation and Syndecan-4 Shedding from Cardiac Cells in Ischemic and Non-Ischemic Heart Disease
Biomedicines, 11 (4)
PubMed 37189684 DOI 10.3390/biomedicines11041066
Rypdal KB, Olav Melleby A, Robinson EL, Li J, Palmero S, Seifert DE, Martin D, Clark C, López B, Andreassen K, Dahl CP, Sjaastad I, Tønnessen T, Stokke MK, Louch WE, González A, Heymans S, Christensen G, Apte SS, Lunde IG (2022)
ADAMTSL3 knock-out mice develop cardiac dysfunction and dilatation with increased TGFβ signalling after pressure overload
Commun Biol, 5 (1), 1392
PubMed 36539599 DOI 10.1038/s42003-022-04361-1
Rixon C, Andreassen K, Shen X, Erusappan PM, Almaas VM, Palmero S, Dahl CP, Ueland T, Sjaastad I, Louch WE, Stokke MK, Tønnessen T, Christensen G, Lunde IG (2022)
Lumican accumulates with fibrillar collagen in fibrosis in hypertrophic cardiomyopathy
ESC Heart Fail, 10 (2), 858-871
PubMed 36444917 DOI 10.1002/ehf2.14234
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