Fredagskollokvium: Can we stop the process of bone formation in heart valves?

Arkady Rutkovskiy, Researcher at the department of Physiology, Institute of Basic Medical Sciences, University of Oslo

The human heart is a pump, which enables circulation of blood by two circuits. One large  

Arkady Rutkovskiy,
Researcher at the department of Physiology,
Institute of Basic Medical Sciences,
UiO. Photo: Gunnar Lothe, UiO

circuit has high pressure and runs through the entire body, the other has low pressure and runs through the lungs. The pump is equipped by four valves, making sure the bood is flowing forward. The valve at the outflow of the major circuit called aortic valve is subjected to the highest pressures and speeds, and in some people it becomes calcified and gets congested, leading to higher workload for the heart and ultimately heart failure. Aortic valve calcification is the most common surgically treated valve disease worldwide. Itbrings about untimely death and reduces quality of life. For now, there are no medical treatments to stop or delay the disease progression, the only available treatment isto replace the aortic valve. However, this treatment is often followed by rapid calcification of a new valve due to unknown reasons. We study the cellular and molecular processes behind aortic valve calcification, which may help to find a non-surgical solution.
The process of aortic valve calcification seems to be similar to the process of bone formation, where cells transform into bone-like cells and produce calcium crystals. To study the mechanisms of this process we used cells isolated from human aortic valves which we obtained during valve replacement surgeries. We studied the interplay between different factors involved in aortic valve calcification and cell transformation including mechanical stress, inflammatory signals and composition of extracellular matter. Additionally, we found that the cells from “sick” calcified valves have changed their phenotype and function compared to cells from healthy valves. Under stimulation with specific factors the cells from healthy valves transformed into different cell lineages similar to stem cells, whereas cells from calcified valves were committed to transform only into bone-like cells. In the course of this project we had to read a ton, make some friends, travel to upstate New York pig farm, attempt gamma-radiation experiments on mice, learn the intricacies of biological ethics in Norway and destroy some bioreactors. Our findings probably represent one small step forward in the identification of potential targets to prevent, inhibit or maybe reverse heart valve calcification, which as far as the biomedical research goes, is pretty good. We will be happy to share the steps of our journey and discuss our science with you!

A current understanding of the pathological differentiation of valvular interstitial cells in aortic valve calcification. The cell types are given in blue. Quiescent valvular interstitial cels (VICs) as an effect of exogenous stimuli (given in yellow fields) differentiate into myofibroblasts (left) or preosteoblasts (right). Differentiation process is shown as gray arrows. Credits: Rutkovskiy A, Malashicheva A, Sullivan G, Bogdanova M, Kostareva A, Stensløkken KO, Fiane A, Vaage J.J Am Heart Assoc. 2017 Sep 14;6(9).


Publisert 9. okt. 2019 09:45 - Sist endret 13. jan. 2020 10:19