MAIN RESULTS:

1. Mechanical stress and inflammation synergistically increase calcification in aortic valve cells.
2. The capacity to differentiate into other cell types is limited in cells from calcified valves.

THESIS DEFENCE:

Thesis: Cellular and molecular mechanisms of human aortic valve calcification
Candidate: Mariia Bogdanova
Time: November 22, 2019 at 13:15
Place: Oslo University Hospital, Rikshospitalet: Store auditorium
Link to university website

SUMMARY:

(1) Bogdanova and her co-workers established and optimized methods to study human aortic valve calcification in vitro.

(2) Mechanical stretch and inflammatory signals caused by lipopolysaccharide increase aortic calcification in synergy by triggering the expression of osteogenic genes. This happens in the extracellular matrix of the aortic side of the valve. The experiments include interstitial cells isolated from healthy and calcified human aortic valves.

(3) Cells from calcified valves have lower potential to differentiate into adipogenic pathway and lower expression of stem cell-associated markers, when compared to cells from healthy valves.

(4) Bogdanova and her colleagues also suggest a possible therapeutic treatment that may prevent or inhibit ongoing calcification in the aortic valves. 

REFERENCES:

(1) Rutkovskiy, A., Malashicheva, A., Sullivan, G., Bogdanova, M., Kostareva, A., Stensløkken, K. O., Fiane, A. & Vaage, J. (2017). Valve interstitial cells: the key to understanding the pathophysiology of heart valve calcification. Journal of the american heart association, 6(9), e006339.

(2) Bogdanova, M., Kostina, A., Zihlavnikova Enayati, K., Zabirnyk, A., Malashicheva, A., Stensløkken, K. O., Sullivan, G. J., Kaljusto, M.-L., Kvitting, J.-P. E., Kostareva, A., Vaage, J., & Rutkovsky, A. (2018). Inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells. Frontiers in physiology, 9, 1635.

(3) Bogdanova, M., Zabirnyk, A., Malashicheva, A., Enayati, K. Z., Karlsen, T. A., Kaljusto, M. L., Kvitting, J.-P. E., Dissen, E., Sullivan, G. J., Kostareva, A., Stensløkken, K. O., Rutkovsky, A., & Vaage, J. (2019). Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties. Scientific reports, 9(1), 1-13.