• 3-Weeks of Exercise Training Increases Ischemic-Tolerance in Hearts From High-Fat Diet Fed Mice 

      Boardman, Neoma Tove; Rossvoll, Line; Lund, Jim; Hafstad, Anne Dragøy; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-02)
      Physical activity is an efficient strategy to delay development of obesity and insulin resistance, and thus the progression of obesity/diabetes-related cardiomyopathy. In support of this, experimental studies using animal models of obesity show that chronic exercise prevents the development of obesity-induced cardiac dysfunction (cardiomyopathy). Whether exercise also improves the tolerance to ...
    • Administration of tetradecylthioacetic acid (TTA) stimulates myocardial fatty acid oxidation despite having a lipid-lowering effect 

      Severson, DL; Hafstad, Anne Dragøy; Khalid, Ahmed Murtaz; Clarke, Kieran; Hagve, Martin; Berge, Rolf; Lund, trine; Larsen, Terje; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2009)
    • Diet-induced obese mouse hearts tolerate an acute high fatty acid exposure that also increases ischemic tolerance 

      Boardman, Neoma Tove; Pedersen, Tina Myhre; Rossvoll, Line; Hafstad, Anne Dragøy; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-03)
      An ischemic insult is accompanied by an acute increase in circulating fatty acid (FA) levels, which can induce adverse changes related to cardiac metabolism/energetics. Although chronic hyperlipidemia contributes to the pathogenesis of obesity-/diabetes-related cardiomyopathy, it is unclear how these hearts are affected by an acute high FA-load. We hypothesize that adaptation to chronic FA exposure ...
    • Effects of high intensity interval training on pregnant rats, and the placenta, heart and liver of their fetuses. 

      Songstad, Nils Thomas; Kaspersen, Knut-Helge; Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-13)
      Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. <p>Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) ...
    • Guidelines on models of diabetic heart disease 

      Heather, Lisa C.; Hafstad, Anne Dragøy; Halade, Ganesh V.; Harmancey, Romain; Mellor, Kimberley M.; Mishra, Paras K.; Mulvihill, Erin E.; Nabben, Miranda; Nakamura, Michinari; Rider, Oliver J.; Ruiz, Matthieu; Wende, Adam R.; Ussher, John R. (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-08)
      Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact ...
    • How Exercise May Amend Metabolic Disturbances in Diabetic Cardiomyopathy 

      Hafstad, Anne Dragøy; Boardman, Neoma Tove; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-04-28)
      Significance: Over-nutrition and sedentary lifestyle has led to a worldwide increase in obesity, insulin resistance, and type 2 diabetes (T2D) associated with an increased risk of development of cardiovascular disorders. Diabetic cardiomyopathy, independent of hypertension or coronary disease, is induced by a range of systemic changes and may through multiple processes result in functional and ...
    • Intracellular MMP-2 Activity in Skeletal Muscle is Associated with Type II Fibers 

      Hadler-Olsen, Elin Synnøve; Solli, Ann Iren; Hafstad, Anne Dragøy; Winberg, Jan-Olof; Uhlin-Hansen, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2014-09-29)
      Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme implicated in motility, differentiation, and regeneration of skeletal muscle fibers through processing of extracellular substrates. Although MMP-2 has been found to be localized intracellularly in cardiomyocytes where the enzyme is thought to contribute to post-ischemic loss of contractility, little is known about intracellular MMP-2 activity ...
    • Isolated perfused working hearts provide valuable additional information during phenotypic assessment of the diabetic mouse heart 

      Pedersen, Tina Myhre; Boardman, Neoma; Hafstad, Anne Dragøy; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-10-01)
      Although murine models for studying the development of cardiac dysfunction in diabetes mellitus are well established, their reported cardiac phenotypes vary. These reported divergences may, in addition to the severity of different models, also be linked to the methods used for cardiac functional assessment. In the present study, we examined the functional changes using conventional transthoracic ...
    • Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise 

      Hancock, Matthew; Hafstad, Anne Dragøy; Nabeebaccus, Adam A.; Catibog, Norman; Logan, Angela; Smyrnias, Ioannis; Hansen, Synne Simonsen; Lanner, Johanna; Schröder, Katrin; Murphy, Michael P.; Shah, Ajay M.; Zhang, Min (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-27)
      Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROSgenerating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels ...
    • NADPH oxidase 2 mediates myocardial oxygen wasting in obesity 

      Hafstad, Anne Dragøy; Hansen, Synne Simonsen; Lund, Jim; Santos, Celio X.C.; Boardman, Neoma Tove; Shah, Ajay M.; Aasum, Ellen (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-02-19)
      Obesity and diabetes are independent risk factors for cardiovascular diseases, and they are associated with the development of a specific cardiomyopathy with elevated myocardial oxygen consumption (MVO<sub>2</sub>) and impaired cardiac efficiency. Although the pathophysiology of this cardiomyopathy is multifactorial and complex, reactive oxygen species (ROS) may play an important role. One of the ...
    • Nox4 regulates InsP3 receptor‐dependent Ca2+ release into mitochondria to promote cell survival 

      Beretta, Matteo; Santos, Celio X.C.; Molenaar, Chris; Hafstad, Anne Dragøy; Miller, Chris CJ; Revazian, Aram; Betteridge, Kai; Schröder, Katrin; Streckfuß-Bömeke, Katrin; Doroshow, James H; Fleck, Roland A; Su, Tsung-Ping; Belousov, Vsevelod; Parsons, Maddy; Shah, Ajay M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-08-10)
      Cells subjected to environmental stresses undergo regulated cell death (RCD) when homeostatic programs fail to maintain viability. A major mechanism of RCD is the excessive calcium loading of mitochondria and consequent triggering of the mitochondrial permeability transition (mPT), which is especially important in post‐mitotic cells such as cardiomyocytes and neurons. Here, we show that stress‐induced ...
    • Overexpression of NOX2 Exacerbates AngII‐Mediated Cardiac Dysfunction and Metabolic Remodelling 

      Hansen, Synne; Pedersen, Tina Myhre; Marin, Julie; Boardman, Neoma Tove; Shah, Ajay M.; Aasum, Ellen; Hafstad, Anne Dragøy (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-01-10)
      The present study aimed to examine the effects of low doses of angiotensin II (AngII) on cardiac function, myocardial substrate utilization, energetics, and mitochondrial function in C57Bl/6J mice and in a transgenic mouse model with cardiomyocyte specific upregulation of NOX2 (csNOX2 TG). Mice were treated with saline (sham), 50 or 400 ng/kg/min of AngII (AngII50 and AngII400) for two weeks. In ...
    • The role of NADPH oxidases in diabetic cardiomyopathy 

      Hansen, Synne Simonsen; Aasum, Ellen; Hafstad, Anne Dragøy (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-25)
      Systemic changes during diabetes such as high glucose, dyslipidemia, hormonal changes and low grade inflammation, are believed to induce structural and functional changes in the cardiomyocyte associated with the development of diabetic cardiomyopathy. One of the hallmarks of the diabetic heart is increased oxidative stress. NADPH-oxidases (NOXs) are important ROS-producing enzymes in the cardiomyocyte ...
    • Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2a-mediated stress signaling 

      Santos, Celio X.C.; Hafstad, Anne Dragøy; Beretta, Matteo; Zhang, Min; Molenaar, Chris; Kopec, Jola; Fotinou, Dina; Murray, Thomas V.; Cobb, Andrew M.; Martin, Daniel; Zeh Silva, Maira; Anilkumar, Narayana; Schröder, Katrin; Shanahan, Catherine M.; Brewer, Alison C.; Brandes, Ralf P.; Blanc, Eric; Parsons, Maddy; Belousov, Vsevelod; Cammack, Richard; Hider, Robert C.; Steiner, Roberto A.; Shah, Ajay M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-01-07)
      Phosphorylation of translation initiation factor 2α (eIF2α) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine–threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2α phosphorylation enhances cell survival. Here, we show ...