The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Professor Christoph Maack, Universitätsklinikum Würzburg
- Second opponent: Professor Anne Jonassen, NTNU, Gjøvik
- Third member and chair of the evaluation committee: Professor Hesso Farhan, University of Oslo
Chair of the Defence
Professor Håvard Attramadal, University of Oslo
Principal Supervisor
Professor Kåre-Olav Stensløkken, University of Oslo
Summary
Ischemic heart disease and myocardial infarction increase the risk to develop fatal heart failure via myocardial remodeling, partly caused by sterile inflammation.
During myocardial infarction, cardiac cells die and release pro-inflammatory factors, like mitochondrial DNA (mtDNA). Mitochondria are abundant in the myocardium and extracellular mtDNA lead to innate immunity activation, sterile inflammation, and damage amplification. mtDNA trigger inflammation via Toll-like receptor 9 (TLR9). Another regulator of the immune system is p66ShcA, a stress-sensitive protein involved in oxidative stress and ischemic tissue damage.
This work investigated the role of TLR9 and p66ShcA in myocardial remodeling after myocardial infarction. We investigated samples from patients with ischemic heart disease and during coronary artery bypass surgery. Animal models with in vivo myocardial infarction from wild type and p66ShcA knockout mice were used.
Cardiac p66ShcA and TLR9 were upregulated post-infarction. The p66ShcA knockout mice had improved healing, reduced oxidative stress, and down-regulation of TLR9 in the myocardium post-infarction. The p66ShcA was a positive upstream regulator of TLR9 signaling. Finally, mtDNA was released into the bloodstream and may be an important contributor to the whole-body inflammation in patients with ischemic heart disease undergoing coronary artery bypass surgery.
These findings suggest that p66ShcA-TLR9 signaling and mtDNA leakage are involved in sterile inflammation, myocardial remodeling, and oxidative stress during and after myocardial infarction and surgical treatment of myocardial ischemia.
Additional information
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