Tønnesen group: Myocardial remodeling and reverse remodeling in pressure overload

Tønnessen group

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

Group members

Latest publications

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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
PubMed 36444917 DOI 10.1002/ehf2.14234
Rypdal KB, Erusappan PM, Melleby AO, Seifert DE, Palmero S, Strand ME, Tønnessen T, Dahl CP, Almaas V, Hubmacher D, Apte SS, Christensen G, Lunde IG (2021)
The extracellular matrix glycoprotein ADAMTSL2 is increased in heart failure and inhibits TGFβ signalling in cardiac fibroblasts
Sci Rep, 11 (1), 19757
PubMed 34611183 DOI 10.1038/s41598-021-99032-2
Frisk M, Le C, Shen X, Røe ÅT, Hou Y, Manfra O, Silva GJJ, van Hout I, Norden ES, Aronsen JM, Laasmaa M, Espe EKS, Zouein FA, Lambert RR, Dahl CP, Sjaastad I, Lunde IG, Coffey S, Cataliotti A, Gullestad L, Tønnessen T, Jones PP, Altara R, Louch WE (2021)
Etiology-Dependent Impairment of Diastolic Cardiomyocyte Calcium Homeostasis in Heart Failure With Preserved Ejection Fraction
J Am Coll Cardiol, 77 (4), 405-419
PubMed 33509397 DOI 10.1016/j.jacc.2020.11.044
Herum KM, Romaine A, Wang A, Melleby AO, Strand ME, Pacheco J, Braathen B, Dunér P, Tønnessen T, Lunde IG, Sjaastad I, Brakebusch C, McCulloch AD, Gomez MF, Carlson CR, Christensen G (2020)
Syndecan-4 Protects the Heart From the Profibrotic Effects of Thrombin-Cleaved Osteopontin
J Am Heart Assoc, 9 (3), e013518
PubMed 32000579 DOI 10.1161/JAHA.119.013518
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