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Endothelial plasticity in fibrosis and epigenetics as a therapeutic target

PhD ceremony:Ms M.S. (Melanie) Hulshoff
When:December 07, 2020
Supervisors:prof. dr. M.C. (Martin / Marco) Harmsen, prof. dr. E.M. Zeisberg
Co-supervisor:dr. G. (Guido) Krenning
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Endothelial plasticity in fibrosis and epigenetics as a therapeutic

Endothelial cells are cells that are lining blood vessels and are in direct contact with the blood. These cells are important because they form a barrier between the blood and adjacent tissues. However, different stimuli can damage these endothelial cells, turning them into more elongated (mesenchymal) cells which are starting to secrete different substances. This leads to a loss of barrier function and contributes to various diseases such as heart and kidney diseases.This change from endothelial cells to more elongated (mesenchymal) cells occurs when certain genes are switched 'on' while others are switched off. This switching on and off of genes is regulated by a group of proteins and is called epigenetics.In this thesis, we investigate how these proteins (epigenetics) influence the transformation of endothelial cells into more elongated (mesenchymal) cells. An overview is provided of all proteins that play a role in this, and new proteins are discovered that may play a role in this.Finally, in this thesis, therapies are developed to change these proteins (epigenetics), which leads to the reduction of heart and kidney diseases in mice. The knowledge gained in this thesis can hopefully also be applied to humans in the future.