p66ShcA Archives - NORHEART

The role of toll-like receptor 9 and the stress-sensitive protein p66ShcA in myocardial remodeling after myocardial infarction has been the focus of Anton Baysa‘s PhD thesis.

MAIN RESULTS:

Deletion of p66ShcA improves short-term survival in myocardial infarction mice.
p66ShcA regulates signaling of toll-like receptor 9.
Mitochondrial and nuclear DNA is released to the bloodstream during coronary artery bypass grafting.

THESIS DEFENCE:

Thesis: The role of p66ShcA and TLR9 signaling in myocardial remodeling and innate immune responses
Candidate: Anton Baysa
Time: November 26, 2020 at 12:15
Place: Online-based solution, due to the covid-19 situation
Link to university website

SUMMARY:

(1) Levels of p66ShcA is increased in the hearts of patients with stable angina, compared to non-failing hearts. p66ShcA is however not increased in explanted hearts with end-stage ischemic heart failure. In mice, expression of p66ShcA increases transiently during the first six weeks after coronary artery ligation.

Mice without p66ShcA have improved survival and lower risk of heart rupture after a myocardial infarction. They also experience less oxidative stress and reduced levels of cardiac matrix metalloproteinase 2, dimished reactive fibrosis and left ventricular dilation.

(3) Toll-like recepetor 9 is upregulated following myocardial infarction but downregulated in p66ShcA knockout mice after a coronary artery ligation. p66ShcA regulates signaling of toll-like receptor 9.

(2) Levels of mitochondrial and nuclear DNA in plasma increase gradually during coronary artery bypass surgery. The levels of mitochondrial DNA is 1000-fold higher than nuclear DNA, indicating that mitochondrial DNA could be an important contributor to the systemic inflammation during heart surgery.

REFERENCES:

(1) Baysa, A., Sagave, J., Carpi, A., Zaglia, T., Campesan, M., Dahl, C. P., Bilbija, D., Troitskaya, M., Gullestad, L., Giorgio, M., Mongillo, M., Di Lisa, F., Vaage, J. I., & Valen, G. (2015). The p66ShcA adaptor protein regulates healing after myocardial infarction. Basic research in cardiology, 110(2), 13.

(2) Baysa, A., Fedorov, A., Kondratov, K., Ruusalepp, A., Minasian, S., Galagudza, M., Popov, M., Kurapeev, D., Yakovlev, A., Valen, G., Kostareva, A., Vaage, J., & Stensløkken, K.-O. (2019). Release of mitochondrial and nuclear DNA during on-pump heart surgery: kinetics and relation to extracellular vesicles. Journal of cardiovascular translational research, 12(3), 184-192.